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Angiographic study and therapeutic embolization of soft-tissue fibrosarcoma in a dog: case report and literature.

A case of soft-tissue fibrosarcoma with pulmonary metastases in a dog is reported. Although three attempts of fine-needle aspiration (FNA) biopsy failed to provide definitive tumor diagnosis, results of angiography strongly indicated a soft-tissue sarcoma. Transcatheter arterial embolization (TAE) using particles of gelatin sponge was performed following selective angiography. The mass was decreased in size on reevaluation 2 weeks after embolization. The dog was euthanized on the request of the owners due to overall failing health. Necropsy and pathological study confirmed the diagnosis of soft-tissue fibrosarcoma with pulmonary metastases. In a review of the literature, angiographic findings of soft-tissue sarcoma in the dog of this report were similar to those in human beings, suggesting a potential role for angiography in the differential diagnosis of suspect soft-tissue fibrosarcomas and for guiding FNA or surgical biopsy. Previous reports have also shown therapeutic embolization to be an effective treatment both in experimental animal study and in clinical practice in the human; therefore, TAE could be an effective adjunctive treatment of soft-tissue fibrosarcoma in the dog.

Animals↗

Diagnosis of primary fibrosarcoma of the lung by fine-needle aspiration and core biopsy.

Primary pulmonary sarcomas are uncommon neoplasms. Primary fibrosarcoma of the lung is extremely rare, and only 53 cases have been documented in the literature to date. To our knowledge, the diagnosis of primary lung fibrosarcoma by fine-needle aspiration cytology has never been reported. We report a case of pulmonary fibrosarcoma diagnosed by fine-needle aspiration cytology and core biopsy. The neoplasm consisted of interweaving fascicles of minimally atypical spindle cells with slender nuclei and scant cytoplasm. Positive immunohistochemistry for vimentin along with nonreactivity of tumor cells for keratin, S100 protein, desmin, alpha-smooth muscle actin, and CD34 supported the the diagnosis. The diagnosis was later confirmed by histologic and ultrastructural findings following lobectomy. A meticulous clinical search for a possible primary neoplasm elsewhere was unsuccessful, and lung was established as the primary site. Fine-needle aspiration cytology and core biopsy are reliable methods for establishing a diagnosis of fibrosarcoma.

Adult↗

Eradication of primary murine fibrosarcomas and induction of systemic immunity by adenovirus-mediated interferon beta gene therapy.

We determined whether an adenoviral vector-mediated murine IFN-beta gene therapy could eradicate established s.c. tumors produced by murine UV-2237m fibrosarcoma cells. The tumor cells were highly susceptible to infection by adenoviral vectors. Cells infected with 10 or 100 multiplicity of infection of AdCIFN-beta, an adenoviral vector encoding murine IFN-beta driven by the human cytomegalovirus promoter, expressed high levels of steady-state IFN-beta mRNA and produced 500 or 7,000 units of IFN-beta activity/10(6) cells/24 h, respectively. Infection of tumor cells with 30 multiplicity of infection of AdCIFN-beta (but not control AdCLacZ vector) inhibited in vitro tumor cell proliferation by 40-45%. Intralesional injection of 5 x 10(8) plaque-forming units of AdCIFN-beta (but not AdLacZ) eradicated established s.c. fibrosarcomas in syngeneic mice but not fibrosarcomas in nude mice. Mice cured of the disease developed systemic immunity against rechallenge with UV-2237m cells but not against another syngeneic tumor, the K-1735 M2 melanoma. Immunohistochemical analysis revealed that tumors injected with AdCIFN-beta contained more macrophages and CD4+ and CD8+ cells than did tumors injected with AdCLacZ or saline. Most cells in the PBS- and AdCLacZ-treated tumors stained positive for proliferating cell nuclear antigen, and few cells stained for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In sharp contrast, AdCIFN-beta-treated tumors contained few proliferating cell nuclear antigen-positive cells and many terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling-positive cells. Taken together, our data demonstrate that IFN-beta gene therapy delivered by adenoviral vectors can be effective against fibrosarcomas.

Adenoviridae↗

[Fibrosarcoma after silicone breast augmentation: is there a connection?].

We describe a 42-year-old woman in whom bilateral fibrosarcoma of the breast was diagnosed 15 years after bilateral breast augmentation with silicone implants. 3 years prior to admission the implants were replaced and 2 years prior to admission mammography showed a nodule in the left breast which biopsy showed to be fibrosarcoma. The implants were removed from both breasts and she was given chemotherapy but later that year underwent bilateral mastectomy. Despite chemotherapy, as well as adjuvant radiotherapy, the disease progressed, with involvement of the lungs and the skin of the left hemithorax. She was admitted repeatedly for severe anemia caused by bleeding from the malignant skin lesions, and died less than 2 years after diagnosis of the disease. Not all reports in the literature find a significant connection between silicone implants and subsequent development of breast cancer, but there are reports that do connect them. Breast fibrosarcoma is not significantly more frequent after silicone augmentation, but still there is controversy as to whether there is a connection between silicone implants and breast malignancy. In the patient we present, the prolonged exposure to silicone may have been a predisposing factor for the development of bilateral fibrosarcoma, since other known risk factors for breast cancer were denied.

Adult↗

Cytodiagnosis of a meningeal fibrosarcoma metastatic to the thyroid gland.

A case of primary leptomeningeal fibrosarcoma metastatic to the thyroid gland, diagnosed by fine needle aspiration biopsy is described. The patient, a 39-year-old women was initially diagnosed with a leptomeningeal fibrosarcoma. Sections of the primary tumor studied by electron microscopy showed that the tumor cells have the ultrastructure features of a fibroblast. She underwent tumor resection, followed by chemotherapy and local radiotherapy. Four months later, she presented with dysphagia. Ultrasonography confirmed the presence of a 2-cm mass in the right lobe of thyroid. A fine needle aspiration biopsy was performed. Light microscopy showed interwoven bundles of neoplastic spindle cells similar to the primary tumor, consistent with a metastatic fibrosarcoma. To our knowledge, this is the first report of a primary meningeal fibrosarcoma that metastasized to the thyroid gland, which was diagnosed by a fine needle aspiration biopsy.

Adult↗

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↗

Loss of mitotic spindle checkpoint activity predisposes to chromosomal instability at early stages of fibrosarcoma development.

Mice carrying the bovine papillomavirus type I genome develop dermal fibrosarcomas in a multiple step process characterized by distinctive proliferative stages. Chromosomal aberrations are identified early in this tumorigenic pathway, however, the mechanism that originates them is unknown. Using a functional assay, we investigated the status of the mitotic spindle cell cycle checkpoint (MSCCC) that regulates the metaphase to anaphase transition, in cells representing different stages of fibrosarcoma progression. Loss of MSCCC activity was apparent in mild fibromatosis and completely abolished in aggressive fibromatosis and fibrosarcoma lesions. This altered MSCCC status was confirmed biochemically by deregulated expression of Cks1 protein and unscheduled cyclin B metabolism. Immunoprecipitation and sequencing analyses indicated that mutation of p53 was not required for the abrogation of the MSCCC. These results demonstrate that loss of mitotic spindle checkpoint activity predisposes to chromosomal instability at early stages of fibrosarcoma development. To our knowledge, these studies constitute the first report of a transition in MSCCC activity in a tumorigenesis model.

Adaptor Proteins, Signal Transducing↗

Absence of ras-gene hot-spot mutations in canine fibrosarcomas and melanomas.

Point mutations within ras proto-oncogenes, particularly within the mutational hot-spot codons 12, 13 and 61, are frequently detected in human malignancies and in different types of experimentally-induced tumours in animals. So far little is known about ras mutations in naturally occurring canine fibrosarcomas or K-ras mutations in canine melanomas. To elucidate whether ras mutations exist in these naturally occurring tumours in dogs, in the present study we screened 13 canine fibrosarcomas, 2 feline fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot-spots, making this the first study to investigate a large number of canine fibrosarcomas. None of the samples showed a K- or N-ras hot spot mutation. Thus, our data strongly suggest that ras mutations at the hot-spot loci are very rare and do not play a major role in the pathogenesis of the spontaneously occurring canine tumours investigated.

Animals↗

Bacopa monniera Linn. extract modulates antioxidant and marker enzyme status in fibrosarcoma bearing rats.

Antioxidative property and tumor inhibitive property of B. monniera (20mg/kg body wt, sc) was examined in 3-methylcholanthrene induced fibrosarcoma rats. Antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and the levels of glutathione (GSH) and the rate of lipid peroxidation (LPO) in the liver and kidney tissues were assessed. A significant increase was noted for the rate of LPO with a corresponding decrease in the antioxidant enzyme status in fibrosarcoma bearing rats. In fibrosarcoma bearing rats, the tumor markers like lactate dehydrogenase (LDH), creatine kinase (CK), alanine transaminase (ALT), aspartate transaminase (AST) and sialic acid (SA) were increased in the serum. Treatment with B. monniera extract significantly increased the antioxidant enzyme status, inhibited lipid peroxidation and reduced the tumor markers. It can be concluded that B.monniera extract promotes the antioxidant status, reduces the rate of lipid peroxidation and the markers of tumor progression in the fibrosarcoma bearing rats.

Animals↗

Effect of intravenous alpha-difluoromethylornithine on the polyamine levels of normal tissue and a transplantable fibrosarcoma.

The effect of a continuous i.v. infusion of alpha-difluoromethylornithine (DFMO) on the polyamine metabolism of tumor and normal host tissue was determined. Non-tumor-bearing Fischer 344 rats or rats bearing a transplantable fibrosarcoma received continuous infusions of DFMO through a central venous catheter at three dose levels. Treatment with DFMO resulted in a time- and dose-dependent, cytostatic effect on the growth of the tumor. In fibrosarcoma-bearing rats the tumor putrescine levels were reduced after 6 and 12 days of DFMO treatment. Tumor spermidine levels were consistently reduced after 6 and 12 days of treatment with the reduction being dose dependent. The decrease in tumor ornithine decarboxylase activity was dose dependent. Erythrocyte putrescine levels were decreased in tumor- and non-tumor-bearing rats, suggesting that DFMO reduces the tumor contribution to the erythrocyte pool. Erythrocyte spermidine levels of fibrosarcoma- and non-tumor-bearing rats were elevated at the lower DFMO doses administered for 12 days but returned to normal as the dose was increased. Erythrocyte spermine levels were elevated in both groups of rats at all DFMO doses. Although normal host tissue weights were not affected by treatment with DFMO, the putrescine and spermidine levels of liver, spleen, and kidney and ornithine decarboxylase activity of the liver and kidney were decreased. These data demonstrate that i.v. DFMO has a cytostatic effect toward a rapidly growing fibrosarcoma associated with the depletion of both tumor putrescine and spermidine levels.

Animals↗

Release of protein bound sialic acid from fibrosarcoma cells after cis-dichlorodiammine platinum (II) treatment: the possible role in tumor regression.

Cis-dichlorodiammine platinum (II) (cisplatin) has been successfully used in experimental immunotherapy of syngeneic transplantable fibrosarcoma in mice. Incubation of fibrosarcoma cells with cisplatin in vitro causes release of sialic acid from tumor cells. The estimation of sialic acid in the supernatant have shown a difference in the release of sialic acid from the tumor cells with different concentrations of cisplatin. The removal of sialic acid from fibrosarcoma cells after cisplatin treatment suggests a possible exposure of certain antigenic sites on the tumor cell surfaces. Such membrane changes may be responsible for the increased antigenicity of fibrosarcoma cells.

Binding Sites↗

[Prognosis in fibrosarcoma of bone].

A retrospective study of 42 patients with bone fibrosarcoma was carried out. A new highly informative index--tumor growth rate--is suggested. It is a ratio of tumor maximum diameter to case history length (Rtg = L, CM/t, month). Three histologically-identified grades of fibrosarcoma malignity are discussed. They are based on the variation in metastasis development and survival rates. As a result of mathematical treatment of the findings, 8 characteristics of bone fibrosarcoma were identified which influenced prognosis. A multi-factorial analysis of the data was undertaken using said characteristics. Indexes were calculated for each characteristic and tabulated to prognosticate 3-year survival of patients with fibrosarcoma of the bone.

Adolescent↗

Glycosaminoglycans and the substrate attachment of murine myeloma, 3T3, and cutaneous fibrosarcoma cells.

The attachment of murine myeloma, 3T3, and cutaneous fibrosarcoma cells to substrates of either fibronectin, type I collagen, or two types of tissue culture plastic was examined in the presence and absence of specific exogenous glycosaminoglycans. Fibrosarcoma and 3T3 cells were found to be nondiscriminatory with respect to their avidity of attachment to substrates of either of the proteins or of conventional tissue culture plastic, whereas the myeloma cells attached significantly less well to a substrate of collagen than to the other two matrices. On tissue culture plastic and collagen the fibrosarcoma cells attached more rapidly than did the other two cell types. Selective and partial inhibition of cell attachment to type I collagen, and, to a lesser extent, fibronectin, occurred upon preincubating these substrates with the sulfated glycosaminoglycans, heparin and heparan sulfate, at concentrations of 1 to 100 micrograms/ml; for 3T3 cells heparin was significantly more inhibitory (mean maximal inhibition of approximately 40%) than were two heparan sulfate fractions. Attachment of fibrosarcoma and 3T3 cells to a nitrogenated tissue culture plastic surface with a net positive charge (Primaria) was nearly 50% inhibited by heparin at the higher concentration and to a lesser extent by the two heparin sulfate fractions. Myeloma cell attachment to this same substrate was inhibited, to a lesser degree, by all three sulfated glycosaminoglycans. Hyaluronic acid, dermatan sulfate, and chondroitin 6-sulfate were inactive in our attachment assays. We suggest that the functional role of glycosaminoglycans in substrate attachment may vary depending on the cell type and the matrix involved in the specific interaction. In particular, the net charge of the substrate appears to be an important factor, and on positively charged surfaces these substances may serve a greater function. However, since nearly complete abrogation of cell attachment should have been achievable by some of the exogenous preparations if cell surface sulfated glycosaminoglycans were to comprise the major cellular binding sites for matrices, we conclude that it is unlikely that these complex polysaccharides function as the principal determinant of simple cell attachment.

Animals↗

Cellular phosphorylation of 1-beta-D-arabinofuranosylcytosine 5-azacytidine with intact fibrosarcoma and leukemic cells.

The phosphorylation of 1-beta-D-arabinofuranosylcytosine (ara-C) and 5-azacytidine (5-aza-C) by A(T1)C1-3 hamster fibrosarcoma cells and L5178Y murine leukemic cells was studied, using intact cells. The cellular phosphorylation of both these nucleoside analogs appears to follow Michaelis-Menton kinetics. The apparent Km value for ara-C in the fibrosarcoma and leukemic cells was about 40 muM, whereas the apparent Km values for 5-aza-C in these cells were about 1.3 and 0.41 mM, respectively. Deoxycytidine and cytidine were found to be potent competitive inhibitors of the phosphorylation of ara-C and 5-aza-C, respectively, ara-C and 5-aza-C were found to be weak competitive inhibitors of the phosphorylation of deoxycytidine and cytidine, respectively. A clone isolated from the fibrosarcoma cells that was partially resistant to the cytotoxic effects of ara-C exhibited a higher Km value for both ara-C and deoxycytidine than the wild-type fibrosarcoma cells.

Animals↗

Two strains of avian sarcoma virus newly isolated from chick fibrosarcomas induced by lymphatic leukemia virus subgroup A in two lines of chickens.

Two strains of avian sarcoma virus, designated S1 and S2, have been newly isolated from avian lymphatic leukemia virus (LLV) subgroup A [LLV(A)]-induced fibrosarcomas in 2 chickens from 2 White Leghorn flocks of lines 151 and BK. Each stock of S1 and S2 contained 2-3 X 10(3) focus-forming units of virus/ml and 10(6) tissue culture infective dose of LLV(A)/ml. The focus-forming titer of S1 and S2 estimated in chick embryo fibroblast cultures was almost consistent with that estimated by tumor (fibrosarcoma) formation in the chicks. All of the chicks bearing wingweb tumors (fibrosarcomas at the site of inoculation) had macroscopically neoplastic lesions (fibrosarcomas) in a number of visceral organs, such as the lung, liver, and spleen. Each stock of S1 and S2 was cloned by picking a single focus, and each focus was examined for the production of focus-forming virus and LLV. The results suggest that S1 and S2 are heterogenous stocks of sarcoma viruses that are replication-defective to various degrees. The low titer of focus-forming virus in the stocks of S1 and S2 was considered to be due to the small amounts of avian sarcoma virus that could be complemented by LLV.

Animals↗

Radiotherapy and hyperthermia in the treatment of fibrosarcomas in the dog.

Ten dogs with oral or external nasal fibrosarcoma were treated sequentially with orthovoltage radiation and radiofrequency (RF)-induced hyperthermia. Total radiation doses ranged from 3,200 to 4,800 rad given in 8 to 12 fractions of 400 rad. Immediately after 2 to 4 radiation treatments, hyperthermia was given. Six oral fibrosarcomas were heated to 50 C for 30 sec, using a hand-held RF generator. Four nasomaxillary fibrosarcomas were heated to 43 C for 30 minutes, using a 500-kHz RF generator. Hyperthermia of 50 C resulted in tumor necrosis and infection in 3 dogs and fatal septicemia in 1 dog. Nine of 10 tumors responded to therapy. One year after therapy, 5 dogs were free of disease. Tumor regrowth occurred in 5 dogs. Mean time to tumor regrowth and mean survival time of all dogs were 343 and 398 days, respectively. The results suggested that sequential radiation-hyperthermia is an effective therapeutic regimen for canine fibrosarcoma. It was concluded that this modality not only may be beneficial in the treatment of canine tumors but may be useful for designing new therapeutic approaches to similar tumors in man.

Animals↗

[Cytotoxic natural anti-tumor antibodies against fibrosarcoma and glioma cells in rats (author's transl)].

The presence of natural anti-tumor antibodies (NAA) against fibrosarcoma- and glioma cells was revealed in the normal sera of 10 different strains of rats. By means of a direct cytotoxicity test using guinea-pig complement and an absorption tests, NAA in inbred WKA/Hok rats were observed to be cytotoxically reactive to all investigated syngeneic and allogeneic fibrosarcoma lines and one glioma line, but not to hepatoma, lymphoma, leukemia, and neurinoma lines. Moreover, NAA reactivity to fibrosarcoma cells was significantly absorbed with brain, lung, kidney, skin homogenates, and cultured normal fibroblasts of syngeneic rats, but not with liver homogenates, thymus, spleen, lymph node and red blood cells. NAA were identified as being predominantly IgM and were stables at 56 degree C for 30 min. With the exception of one strain, there were no strain or sex differences in NAA levels among any of the investigated strains of rats. The level of NAA correlated with the in vivo anti-tumor response: when NAA-reactive fibrosarcoma or glioma cells were implanted into syngeneic WKA/Hok rats, groups of rats with high NAA levels suppressed tumor growth and survived longer than groups of rats with low NAA levels, while there was no difference in length of survival days in NAA non-reactive hepatoma or lymphoma cells. When 3-methylcholanthrene was inoculated into these two groups of rats, the tumor incidence in the groups of rats with high NAA level was significantly suppressed as compared to the group of rats with low NAA level. We discuss the mechanism of the induction of NAA in relation to the anti-tumor immunity.

Age Factors↗

Congenital fibrosarcoma in the oral cavity. First reported case.

Fibrosarcoma is uncommon in the head and neck and constitutes less than 1% of malignancies and approximately 6% of the soft tissue sarcomas. Congenital fibrosarcomas are characterized by rapid proliferation and frequent local recurrence following excision. Unlike other sarcomas, metastasis is a rare event. The literature contains less than 50 cases of congenital, solitary fibrosarcoma, with none occurring in the oral cavity. This paper describes a unique case of fibrosarcoma in the oral cavity of a neonate. A 12 month follow-up is provided with an analysis of the histopathology including electron microscopy. The spectrum of fibroproliferative lesions in the pediatric patient is reviewed, and the evaluation and treatment modalities applicable to this age group are outlined.

Fibrosarcoma↗