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Potentiation by carbon tetrachloride of the immunosuppressive effects of fibrosarcoma and toxic material produced by fibrosarcoma cells.

SaD2-AG fibrosarcomas growing in DBA/2 mice caused nonspecific immunodepression. Injection of soluble material produced by cultured SaD2-AG cells into normal DBA/2 recipients caused nonspecific immunodepression and signs of systemic toxicity. These in vivo effects were enhanced by prior treatment of the recipients with carbon tetrachloride (CCl4). In contrast, material released by syngeneic fibroblasts was neither immunosuppressive nor toxic to normal mice or mice previously treated with CCl4. A soluble toxic material released by the fibrosarcoma cells may be responsible for at least some of the systemic effects of localized SaD2-AG tumors growing at a site not involving vital structures, and a protective host mechanism whose maximum capacity can be decreased by the administration of CCl4 may minimize the toxic effects of the cancer-derived material.

Animals

Studies on the intracellular degradation of newly synthesized collagen in 3-methylcholanthrene induced fibrosarcoma cells.

The intracellular degradation of newly synthesized collagen was studied in both normal fibroblast and 3-methylcholanthrene induced fibrosarcoma cells. The degradation of newly synthesized collagen was examined using pulse-chase experiments and radioactive labelling techniques with [3H]-proline. The percentage of intracellular proteolysis of newly synthesized collagen was determined by measuring the formation of [3H]-hydroxyproline containing fragments in alcohol-soluble and insoluble fractions of normal cells and fibrosarcoma cells in the culture. The rate of degradation of newly formed collagen was then followed by estimating the radioactivity of [3H]-hydroxyproline at different intervals, during the chase period. The results clearly demonstrated that the percent of intracellular degradation of newly synthesized collagen was approximately three fold higher in fibrosarcoma cells than in normal fibroblast cells. The increased intracellular degradation of newly formed collagen was followed by an increase in the activity of cathepsin B and L in fibrosarcoma cells. The pulse-chase experiments indicated that the rate of degradation of newly synthesized collagen in fibrosarcoma cells is relatively greater than in normal fibroblast cells. In addition, as the labelling time increased, the formation of [3H]-hydroxyproline containing peptides in the ethanol-soluble fraction were found to be increased in both normal cells and fibrosarcoma cells, but the extent of formation was higher in fibrosarcoma cells compared to normal fibroblast cells. The results of this investigation collectively suggest that the intracellular degradation of newly synthesized collagen is enhanced in fibrosarcoma cells.

Animals

Infantile and adult fibrosarcomas of the soft tissues.

Histologic sections of 68 soft-tissue sarcomas initially diagnosed as fibrosarcoma were reviewed, and 36 were excluded because of revised diagnosis. The tumors from the remaining 32 patients were analyzed clinicopathologically, and were classifed into two types; the adult type (22 cases) and the infantile type (10 cases). The adult type fibrosarcoma occurred in adults aged 25 to 67 years and consisted of spindle-shaped fibroblastic cells which formed interlacing bundles accompanied by variable amounts of collagen or reticulin fibers. The infantile fibrosarcoma affected children below the age of seven years in this series and was characterized by proliferation of immature fibroblasts forming indistinct bundles, frequently exhibiting areas of an angiosarcoma-like pattern and cavernous blood vessels. The authors expressed the view that infantile fibrosarcoma should be separated from adult fibrosarcoma, because between these two types of fibrosarcoma there were marked differences in the histologic feature as well as in the age, sex and anatomical distributions.

Adult

[Ultrastructural study of fibrosarcoma].

Ultrastructure of 9 cases of fibrosarcoma was observed and compared with that of fibrous connective tissue of 4 human embryos and 9 cases of spindle cell sarcoma, including 3 each of leiomyosarcoma, neurofibrosarcoma and dermatofibrosarcoma protuberans. Ultrastructurally, fibrosarcoma consisted of well-differentiated fibroblast-like cells, poorly differentiated fibroblast-like cells (embryonic fibroblast-like cells), myofibroblast-like cells and primitive mesenchymal cells. It is suggested that fibrosarcoma may arise from primitive mesenchymal cells which are capable of differentiating into fibroblast and myofibroblast. There were two special cases of fibrosarcoma in this series. One was a congenital fibrosarcoma with ultrastructure resembling adult and the other was a sarcoma of myofibroblast. Diagnosis and differential diagnosis between fibrosarcoma and leiomyosarcoma, neurofibrosarcoma, dermatofibrosarcoma protuberans are discussed.

Adolescent

Inhibition of syngeneic fibrosarcoma growth by lymphocytes sensitized on tumor-cell monolayers in the presence of the thymic humoral factor.

The present experiments were performed to investigate the possibility of inhibiting tumor growth in vivo with syngeneic lymphocytes sensitized in vitro on monolayers of the tumor under test, and to study the effect of a thymic humoral factor (THF) in this sensitization process. Monolayers of fibrosarcoma cells were used to sensitize spleen cells from syngeneic donors against the tumor. Such sensitized lymphocytes manifested cytotoxic activity against cells fo the fibrosarcoma in a microassay measuring tumor-cell detachment. However, when the sensitized lymphocytes were mixed with the fibrosarcoma cells and injected into syngeneic mice, enhanced tumor growth was observed in vivo. Addition of thymic humoral factor to the cultures during sensitization resulted in increased cytotoxic activity by the lymphocytes in vitro and a reduction in the tumor enhancement caused by these cells when injected in vivo. Enhanced tumor growth occured when activated lymphocytes of allogeneic as well as syngeneic origin were injected together with the fibrosarcoma cells. Enhancement, which was already apparent when the spleen cells had been sensitized for 24 h, could be circumvented by separate administration of lymphocytes and tumor cells. Syngeneic lymphocytes injected systemically after sensitization for 5 days exerted anti-tumor reactivity against the fibrosarcoma grafted in the foot-pad of syngeneic mice. Tumor growth was further inhibited by systemic injection of lymphocytes which had been sensitized in the presence of the thymic humoral factor.

Animals

Postirradiation fibrosarcoma following radical mastectomy.

A case of fibrosarcoma arising in the scar of the radical mastectomy with postoperative irradiation of breast carcinoma is reported. The tumors arose five times in spite of the extirpations including surrounding tissue since 11 years after radical mastectomy and postoperative irradiation. All of arisen tumors were diagnosed fibrosarcoma histologically and with every recurrence the aggravation of malignancy of tumors was shown. In this case, the primary tumor of the breast was infiltrating carcinoma and no sign of fibrosarcoma was noted histologically. The mastectomy scar was indicated the irradiation therapy postoperatively and fibrosarcoma developed 11 years after postoperative irradiation. Namely, this case agreed to the strict criteria of the postirradiation sarcoma proposed by Cahan et al. In this paper, a case of postirradiation fibrosarcoma arising in the scar of radical mastectomy for carcinoma is presented.

Breast Neoplasms

Transformation of ameloblastic fibroma to fibrosarcoma.

The direct transformation of an ameloblastic fibroma into a fibrosarcoma in a 16-year-old Caucasian male is reported. Although no ameloblastic epithelium was found in the recurrent tumor, the odontogenic origin of the fibrosarcoma was evident. The ameloblastic fibrosarcoma and the fibrosarcoma of identical odontogenic origin represent an entity which should be distinguished from conventional fibrosarcoma as these tumors demonstrate different clinical behaviors.

Adolescent

In vitro induction of tumour-specific immunity V. Detection of common antigenic determinatnts of murine fibrosarcomas.

Two 3-methylcholanthrene and a spontaneous BALB/c fibrosarcoma were examined for tumour-associated antigens (TAA) by in vivo and in vitro induction of tumour-immune responses. When BALB/c mice were immunized to these fibrosarcomas by surgical tumour removal, cross-reacting tumour-associated transplantation antigens (TATA) were detected on all 3 tumours. Cytotoxic effector cells (CL) were then induced in vitro by co-culture of BALB/c spleen cells with the spontaneous, or one of the carcinogen-induced fibrosarcomas. These CL were shown to be cytotoxic T cells (Tc) and to be directed against cross-reacting TAA on all 3 tumours, by two in vitro 51Cr-release assay systems, direct 51Cr-release cytotoxicity and cellular competitive inhibition of 51Cr release. Further studies demonstrated that the fibrosarcoma TAA involved in in vitro induction of Tc were not present on normal adult or foetal tissues. A secondary cytotoxic response was also detected in vitro when spleen cells from mice immunized to a carcinogen-induced fibrosarcoma were tested. The patterns of cross-reactivity detected by the in vivo and primary in vitro tumour-immune responses suggested that the TAA detected in vivo (TATA) were not identical to the TAA detected in vitro.

Animals

Metastatic spread of fibrosarcoma of bone; A report on forty-nine cases, and a comparison with osteosarcoma.

Of tumours arising in otherwise normal bones, fibrosarcoma is about one-third as common as osteosarcoma and may have a very slightly better prognosis. A comparison of the aetiology and behaviour of forty-nine fibrosarcomata and 152 osteosarcomata indicates several similar features. Fibrosarcoma lacks the characteristic peak incidence in adolescence of osteosarcoma, but the age and sex distributions of both tumour types in patients of middle life--twenty-five to sixty-five years--are remarkably similar, even in their frequency. With fibrosarcoma, perhaps, lung metastases are fewer and appear later, thus contributing to the slightly better survival, but there is some increase in the proportion of extra-pulmonary secondaries. As with osteosarcoma, patients with fibrosarcoma show some increase in the length of post-metastatic survival when metastases are of later appearance. For the whole series the five-year crude survival rate was 21 per cent, better results being recorded for patients with histologically well differentiated tumours (30 per cent) and for long bone tumours when the patient was metastasis-free initially and the tumour was treated by prompt ablation (40 per cent). These are probably the best results one may expect for osseous fibrosarcoma without recourse to adjuvant antimetastatic therapy. Complete control of the primary tumour is likewise mandatory, and can be assured only by complete surgical removal when this is technically feasible.

Adolescent

Multiple diffuse fibrosarcoma of bone.

Light and electron microscopic observations of a case of multiple diffuse fibrosarcoma of bone are presented. Two cases of diffuse fibrosarcoma of bone have been previously reported. Clinically the tumor presented as multiple osteolytic lesions involving the pelvis bone, vertebral bodies and skull with the radiologic appearance of a multiple plasma cell myeloma. Histologically the tumor was a spindle-cell fibrosarcoma. At the ultrastructural level the tumor cells represent fibroblasts separated by a scanty amount of collagen fibers. Electron microscopic findings substantiate the fibroblastic origin of multiple diffuse fibrosarcoma of bone.

Bone Neoplasms

Nonepithelial tumors of the nasal cavity, paranasal sinuses, and nasopharynx. A clinicopathologic study. VI. Fibrous tissue tumors (fibroma, fibromatosis, fibrosarcoma).

In a study of 256 nonepithelial neoplasms involving the nasal cavity, paranasal sinuses, and nasopharynx, 23 lesions were classified as fibrous tissue tumors, including four cases of "fibroma", six of fibromatosis, and thirteen of fibrosarcoma. The clinical findings associated with these lesions are described, their histologic features illustrated, results of therapy presented and clinicopathologic correlations made. The "fibromas" presented a small localized nodules. None recurred after local excision. Fibromatosis, a locally aggressive tumor, does not metastasize, but may cause considerable morbidity or even death due to local infiltration which may be difficult to control surgically. Fibrosarcoma may cause death either by local infiltration or by metastasis, but has a better prognosis than most other sarcomas of this region. We recommend that a large en block resection be performed initially for fibromatosis and fibrosarcoma growing in this area, after the diagnosis has been made by biopsy. In this series, including patients who had more than one operation, recurrent tumor was seen following 10 of 12 limited local excisions performed for fibromatosis and fibrosarcoma, but in only one of 13 patients after a large bloc resection. The problems involved in histologically differentiating fibrous tissue tumors from other lesions are discussed. A patient with the rare syndrome of multicentric fibromatosis with spontaneous regression of lesions is presented.

Adult

Genetics of susceptibility in the platyfish/swordtail tumor system to develop fibrosarcoma and rhabdomyosarcoma following treatment with N-methyl-N-nitrosourea (MNU).

About 7000 animals of 65 different genotypes of the xiphophorine fish were treated with the direct acting chemical carcinogen N-methyl-N-nitrosourea (MNU; 10(-3)M; four times for 1 hour in two week intervals), in order to find out whether the susceptibility for development of fibrosarcomas and rhabdomyosarcomas is directly related to the genotype. A genotype specific susceptibility was found, ranging from zero to about nine percent. The highest susceptibles were found in certain backcross hybrids involving P.variatus/X.helleri-hybrids and X.helleri, as the recurrent parent. These genotypes were further analysed. Both P.variatus and X.helleri, as werr as their F1 proved to be insusceptible; while from the three backcrosses, which were tested, namely the BC1, BC4 and BC15, both the BC1, and the BC4, were susceptible, but the BC15 was insusceptible. The results are interpreted on the basis of the assumption that the differential susceptibility is a function of the type of control of a tumor gene (Tu-Fi-Rh) endogenous to P.variatus and involved in development of fibrosarcomas and rhabdomyosarcomas. Accordingly, in P.variatus and in the F1 the Tu-Fi-Rh is controlled by repressing genes (R-genes) linked as well as non-linked to Tu-Fi-Rh; because simultaneous mutation of both R-genes following treatment with MNU is an extremely unlikely event, these genotypes have an extremely low susceptibility. By contrast, in the BC1 and the BC4 the non-linked R-genes become eliminated and only the linked R-gene remains for repression of Tu-Fi-Rh; this condition confers a high degree of susceptibility, because one single mutation may lead to impairment of the R-gene and to Tu-Fi-Rh-mediated formulation of fibrosarcomas and rhabdomysarcomas. In the BC15, furthermore, also the Tu-Fi-Rh has become eliminated, resulting in a loss of the susceptibility. The results suggest that in the xiphophophorine fish the susceptibility for responding to MNU-treatment with the development of fibrosarcomas and rhabdomysarcomas is related directly to the genotype.

Age Factors

Anal fibrosarcoma: report of a case and review of literature.

A unique case of anal fibrosarcoma is reported. Review of the literature in the past half century revealed only 13 cases of rectal fibrosarcoma, and no case of anal fibrosarcoma. Abdominoperineal resection is the usual treatment if the disease is confined to the rectum or anus. An extended resection may be indicated in those patients who have more extensive disease. Long-term follow-up information was not available in the literature. The prognosis is presumed to be the same as if not worse than for fibrosarcomas in other parts of the body. Reporting of this rare tumor when found in unusual locations is encouraged.

Aged

Differential radioprotection of cultured human diploid fibroblasts and fibrosarcoma cells by WR1065.

The present studies were performed to determine whether WR1065, the dephosphorylated, free-thiol active metabolite of WR2721, could provide differential radioprotection of normal and tumor cell lines in vitro and secondly to investigate potential mechanisms for the selective nature of the radioprotection at the cellular and molecular level. When 4 mM WR1065 was administered 30 min prior to and during irradiation, a protection factor of 1.9 was obtained in clonogenic assays performed with normal human diploid fibroblasts (AG1522) while no protection of fibrosarcoma cells (HT1080) was observed. Some radioprotection of fibrosarcoma cells was observed with higher drug concentrations (10-40 mM), but the increase in survival was considerably less than the plateau level reached with the diploid fibroblasts (3-fold vs 24-fold at 6 Gy). The observation of such a selective effect in vitro with WR1065 indicates that differences in tissue-specific variables such as blood flow, pH, pO2, and drug dephosphorylation cannot solely account for the selective nature of the radioprotection afforded by WR2721 in vivo. Incubation of nucleoids with increasing concentrations of the DNA intercalating dye propidium iodide was used to titrate the ability of DNA to undergo supercoiling changes. The relaxation and rewinding of supercoiled DNA loops in isolated nucleoids serves as an indicator of both the presence of DNA damage and inherent differences in DNA loop characteristics. Fibrosarcoma cells had a much larger propidium iodide-relaxable DNA loop size than fibroblasts. The rewinding phase of the DNA supercoiling response is impaired by the presence of radiation-induced DNA strand breaks. Four mM WR1065 resulted in a significant reduction in the amount of rewinding inhibition observed after a dose of 10 Gy in diploid fibroblasts (protection factor = 1.43) but did not alter the response of irradiated fibrosarcoma cells. These results, indicating that WR1065 had a preferential radioprotective effect in vitro on both survival and the manifestation of DNA damage at the nucleoid level, are consistent with the hypothesis that cell type differences in chromatin organization and DNA-drug associations could play a role in the selective radioprotection.

Cell Survival

Fibrosarcoma of bone. A demographic, clinical and histopathological study of all cases recorded in the Swedish cancer registry from 1958 to 1968.

The clinical records, radiographs and histopathological material of all forty-one patients recorded as suffering from fibrosarcoma of bone in the Swedish Cancer Registry for the years 1958 to 1968 have been analysed; in addition, four cases were found on histological review of a series of osteosarcomas. From this re-examination, twenty-four patients with genuine fibrosarcoma of bone were identified; twenty-two had primary neoplasms and two secondary. No sex or geographical differences were found. The tumours showed a prevalence for patients in the adult and older age groups. Half of the tumours arose from femoral or tibial metaphysial bone adjacent to a knee joint. All the tumours were of the medullary type. Almost one-third presented with a pathological fracture, and soft-tissue extension had occurred in all but three tumours. In contrast to previous reports, these tumours were more malignant than osteosarcomas and showed a five-year survival rate of only 4-2 per cent. In accessible sites, ablative surgery was used as the primary treatment, Fibrosarcoma of bone is a distinctive lesion and should be distinguished carefully from periosteal and soft-tissue fibrosarcomas because of differences in prognosis and treatment.

Biopsy, Needle

Embryonic antigens shared between chemically induced lymphosarcomas and fibrosarcomas of the mouse.

An antiserum obtained by the immunization of C57BL/HeDp mice with a pool of C3HF/Dp 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced fibrosarcomas exerted a specific cytotoxic activity in vitro on C57BL/HeDp chemically induced lymphosarcomas. Conversely, C57BL/HeDp spleen cells sensitized against C3Hf/Dp chemically induced lymphosarcomas or embryo cells were cytotoxic for plated cells of syngeneic DMBA-induced fibrosarcomas. Absorption studies with antiembryo and antilymphoma antisera showed that embryonic antigens were shared between lymphosarcomas and fibrosarcomas and that all serologically defined antigens present on lymphoma cells, including virus-related antigens, were also on fibrosarcoma cells.

Animals