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At least 19 recordsLinked to original sources

Fibrosarcomas at presumed sites of injection in dogs: characteristics and comparison with non-vaccination site fibrosarcomas and feline post-vaccinal fibrosarcomas.

Fifteen fibrosarcomas, surgically excised from presumed sites of injection in dogs, and 10 canine fibrosarcomas excised from sites not used for injection were histologically and immunohistochemically compared with 20 feline post-vaccinal fibrosarcomas. Canine fibrosarcomas from presumed injection sites were of grade I (3), of grade II (4) and grade III (8). Two fibrosarcomas from non-injection sites were of grade I, four of grade II and four of grade III. Feline samples were classified as grade I (2), grade II (4) and grade III (14). All fibrosarcomas from presumed injection sites of both species showed lymphocytic inflammatory infiltration located at the tumour periphery, while two canine fibrosarcomas from non-injection sites showed perivascular inflammatory infiltration within the neoplasm. All samples were immunohistochemically examined for vimentin, smooth muscle actin, muscle specific actin and desmin expression. All tumours were positive for vimentin. Ten canine fibrosarcomas from presumed injection sites and all feline samples contained cells consistent with a myofibroblastic immunophenotype. Aluminium deposits were detected in eight canine fibrosarcomas from presumed injection sites and 11 feline post-vaccinal fibrosarcomas by the aurintricarboxylic acid method. The present study identifies distinct similarities between canine fibrosarcomas from presumed injection sites and feline post-vaccinal fibrosarcomas, suggesting the possibility of the development of post-injection sarcomas not only in cats, but also in dogs.

Animals↗

Low-grade fibrosarcoma--report on 39 not otherwise specified cases and comparison with defined low-grade fibrosarcoma types.

AIMS: Low-grade fibrosarcomas are tumours that mainly affect the extremities and trunk of adults of either sex. Among these, low-grade fibromyxoid sarcoma (FMS), hyalinizing spindle cell tumour with giant collagen rosettes (HST) and sclerosing epithelioid fibrosarcoma (SEF) are well-established entities. In this study, our aim was to describe a group of low-grade fibrosarcomatous tumours, which could not be encompassed by these entities. These low-grade fibrosarcomas, not otherwise specified (FNOS) were provisionally designated as 'fibrosarcoma, low-grade fibroblastic type'. METHODS AND RESULTS: In the soft tissue tumour registry we found 39 FNOS (46%), 31 FMS (36%), 11 SEF (13%) and four HST (5%). FNOS occurred in older patients than FMS (mean age 56.3 years versus 33.7 years). They mainly showed fibrous features, but myxoid areas could also be seen. While cells tended to be loosely arranged in the myxoid areas, densely packed sheets with a storiform pattern, fascicular arrangements or regions without a defined growth pattern were observed in the fibrous areas. However, neither whirling nor swirling patterns were found. Arcade-like vessels were not visible; pseudolipoblasts did not occur. FNOS exhibited increased atypia and mitotic count compared with the other sarcomas studied [FNOS, mean value 4.6 mitoses/10 high-power field (HPF); FMS, 0.7/10 HPF). Follow-up data were available in 21 FNOS patients. In seven cases (33.3%), local recurrences were reported. Three patients (14.3%) developed metastases and all of them died of tumour. CONCLUSIONS: The term 'fibrosarcoma, low-grade fibroblastic type' should be used as a diagnosis of exclusion. Further studies should elucidate whether it represents a distinct fibrosarcoma type.

Adult↗

Response rate of fibrosarcoma cells to cytotoxic drugs on the expression level correlates to the therapeutic response rate of fibrosarcomas and is mediated by regulation of apoptotic pathways.

BACKGROUND: Because of the high resistance rate of fibrosarcomas against cytotoxic agents clinical chemotherapy of these tumors is not established. A better understanding of the diverse modes of tumor cell death following cytotoxic therapies will provide a molecular basis for new chemotherapeutic strategies. In this study we elucidated the response of a fibrosarcoma cell line to clinically used cytostatic agents on the level of gene expression. METHODS: HT1080 fibrosarcoma cells were exposed to the chemotherapeutic agents doxorubicin, actinomycin D or vincristine. Total RNA was isolated and the gene expression patterns were analyzed by microarray analysis. Expression levels for 46 selected candidate genes were validated by quantitative real-time PCR. RESULTS: The analysis of the microarray data resulted in 3.309 (actinomycin D), 1.019 (doxorubicin) and 134 (vincristine) probesets that showed significant expression changes. For the RNA synthesis blocker actinomycin D, 99.4% of all differentially expressed probesets were under-represented. In comparison, probesets down-regulated by doxorubicin comprised only 37.4% of all genes effected by this agent. Closer analysis of the differentially regulated genes revealed that doxorubicin induced cell death of HT1080 fibrosarcoma cells mainly by regulating the abundance of factors mediating the mitochondrial (intrinsic) apoptosis pathway. Furthermore doxorubicin influences other pathways and crosstalk to other pathways (including to the death receptor pathway) at multiple levels. We found increased levels of cytochrome c, APAF-1 and members of the STAT-family (STAT1, STAT3), while Bcl-2 expression was decreased. Caspase-1, -3, -6, -8, and -9 were increased indicating that these proteases are key factors in the execution of doxorubicin mediated apoptosis. CONCLUSION: This study demonstrates that chemotherapy regulates the expression of apoptosis-related factors in fibrosarcoma cells. The number and the specific pattern of the genes depend on the used cytotoxic drug. The response rates on the gene expression level, i.e. the number of genes regulated by the drugs actinomycin D, doxorubicin and vincristine, correlate to the clinical effectiveness of the drugs. Doxorubicin seems to exert its cytotoxic mechanism by regulating genes, which are involved in several different apoptosis regulating pathways. The exact knowledge of the genes affected by the drugs will help to understand the diverse modes of soft tissue sarcoma cell death in response to cytotoxic therapies.

Antibiotics, Antineoplastic↗

Sclerosing epithelioid fibrosarcoma. A variant of fibrosarcoma simulating carcinoma.

We report 25 cases of a peculiar sclerosing epithelioid variant of fibrosarcoma (SEF) simulating an infiltrating carcinoma. The tumors occurred primarily in the deep musculature and were frequently associated with the adjacent fascia or periosteum. The patients' ages were 14 to 87 years (median, 45). Fourteen were male and 11 female. The tumors were located in the lower extremities and limb girdles (12 cases), trunk (9), upper limb girdles (2), and neck (2). They measured 2 to 14.5 cm in greatest dimension (median size, 7 cm) and were gray to white and firm. Histologically, the lesions were characterized by a proliferation of rather uniform, small, slightly angulated, round to ovoid epithelioid cells with sparse, often clear cytoplasm arranged in distinct nests and cords. In all cases there was prominent hyaline sclerosis, sometimes reminiscent of osteoid or cartilage and foci of conventional fibrosarcoma. Occasional myxoid zones with cyst formation and foci of hyaline cartilage, calcification, and metaplastic bone were also seen. Mitotic figures were generally scarce. Vimentin was detected in 13 of 14 cases, epithelial membrane antigen in seven, S100 protein in four, and neuron-specific enolase in two. Cytokeratins were detected with AE1/AE3 and CAM 5.2 in two cases. Leukocyte common antigen, CD68 antigen, HMB45, desmin, and alpha-smooth muscle actin were negative in all cases. In 13 of 14 cases, 75% or more of the cells stained for proliferating cell nuclear antigen (PCNA). Ki67 immunostaining with MIB 1 showed low proliferative activity in all cases, averaging 5% of tumor cells or less. In all cases, p53 was detected by immunohistochemical methods; bcl-2, an antiapoptosis marker, was detected in more than 90% of the cells in 11 of 12 cases. Ultrastructurally, both the epithelioid and spindled tumor cells had features of fibroblasts. Follow-up in 16 cases ranging from 13 months to 17 years 3 months (median, 11 years 4 months) revealed persistent disease or local recurrences in 53% of patients and metastases in 43%. The metastases were to the lungs (4 cases), skeleton (3), chest wall/pleura (3), pericardium (1), and brain (1). Four patients died of disease, four were alive with disease, two were known to be alive but disease status unknown, and six had no evidence of further disease at last follow-up. The data suggest that SEF is a relatively low-grade fibrosarcoma; yet it is fully malignant despite the presence of histologically benign-appearing foci. The proliferation markers PCNA and Ki67 did not correlate with prognosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Sclerosing epithelioid fibrosarcoma: a fibrosarcoma with a very long course].

Sclerosing epithelioid fibrosarcoma is a rare and slowly growing variant of fibrosarcoma occurring in adults. Its carcinomatous and/or hemangiopericytomatous patterns may mislead to many different tumors. These differential diagnoses are generally ruled out by the clinical data, the morphology and the immunohistochemical study. We report two typical cases of this fibrosarcoma and we highlight the different criterias which are indispensable to make the diagnosis. The very slow course of this disease goes along with a very low proliferative rate, but an accumulation of p53 by immunohistochemistry is paradoxically always founds, even though this accumulation is more often found in highly aggressive sarcomas.

Adult↗

Pedunculated fibrosarcoma. Unusual presentation of an intraabdominal fibrosarcoma arising from the greater omentum.

A 50 year old man presented with lower abdominal pain and hypotension of sudden onset. Emergency laparotomy for a suspected ruptured abdominal aortic aneurysm revealed the source of hemorrhage to be a ruptured vessel in the vascular pedicle of a large, oval tumor. This tumor had a unique appearance, lying virtually free within the abdominal cavity except for a 17 cm long umbilical cord-like vascular attachment to the greater omentum and a single fibrous adhesion to the anterior abdominal wall. Histologic examination disclosed the features of fibrosarcoma with a prominent population of myofibroblasts. Review of the literature yielded no previous examples of a similar pedunculated fibrosarcoma.

Abdominal Neoplasms↗

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↗

Analysing collisions between fibroblasts and fibrosarcoma cells: fibrosarcoma cells show an active invasionary response.

We describe a direct way of measuring contact inhibition of locomotion by analysing the changes in motion of pairs of colliding cells. This allows values to be assigned to each type of cell in mixed collisions and will enable certain hypotheses about the relationship between contact inhibition and invasion in culture to be tested critically. We find that fibrosarcoma (FS9) cells, on colliding with chick heart fibroblasts, show a reversed contact-inhibition response that we call contact promotion of locomotion. We also describe a measure of the lateral changes in motion that result from collisions between cells and show that this is dependent on the type of colliding cell but, unlike contact inhibition, it does not appear to be dependent on the type of cell with which it collides for the types studied here. Finally, we analyse how the total response is dependent on the dispositions and motions of the cells before collision and we find that FS9 cells, on colliding with fibroblasts, tend to turn towards the point of initial marginal contact. We conclude that the FS9 cells show a pronounced response on colliding with the fibroblasts, which is in contrast to the subjective impression that the FS9 cells do not respond much. These findings support the thesis of Abercrombie and colleagues, that the infiltration of a population of normal cells by a population of invasive cells in culture is dependent on the nature of the response of each cell type to collision with the other and that the invasive cells fail to show contact inhibition in these heterotypic collisions; but the findings further suggest that these invasive cells show an active invasionary response as opposed to merely failing to show contact inhibition.

Animals↗

Adoptive transfer of immunity against solid fibrosarcoma in mice with splenocytes and peritoneal exudate cells obtained after in vitro sensitization and in vivo immunization with cis-dichlorodiamine platinum(II) treated fibrosarcoma cells.

Co-cultivation of splenocytes with cis-dichlorodiamine platinum (II) treated tumor cells generate cytotoxic splenocytes, which when injected into normal mice, render them resistant to tumor challenge. Significant increases in mean survival time and 33% of tumor free survivals were observed in mice exposed to a tumor challenge on the 10th day after injection of sensitized splenocytes. Splenocytes peritoneal exudate cells obtained after in vivo immunization of mice with cis-dichlorodiamine platinum(II) treated cells retarded tumor growth in vivo when injected in different combinations in tumor bearing mice. Maximum survival time of tumor bearing mice and 20% tumor free survivals were observed when the animals were injected with a combination of immune splenocytes and normal peritoneal exudate cells. The increase in the number of macrophages of immunotherapeutically treated mice suggests that host macrophages have been activated. Splenocytes and macrophages obtained from immunotherapeutically treated mice showed an increase in cytotoxicity against tumor cells in vitro.

Animals↗

Feline fibrosarcomas at vaccination sites and non-vaccination sites.

A retrospective study of 195 feline sarcomas diagnosed histologically between July 1988 and June 1994 showed that 170 (87.2%) were fibrosarcomas. Cats with vaccination site (VS) fibrosarcomas were younger (8.6 +/- 3.9 years; median = 8 years) than cats with non-vaccination site (NVS) fibrosarcomas (10.2 +/- 4.7 years; median = 11 years) (P = 0.03), but there was no such association with breed, sex, or "neuter status". Microscopical features more characteristic of VS fibrosarcomas than of NVS fibrosarcomas were (1) subcutaneous location (P < 0.001), (2) necrosis (P < 0.001), (3) inflammatory cell infiltration (P < 0.001), (4) increased mitotic activity (P < 0.02), (5) pleomorphism (P < 0.001), and (6) variability in the density of the extracellular matrix (P < 0.001). When these data were fitted to a logistic regression model, younger age (P = 0.003), subcutaneous location of the fibrosarcoma (P = 0.0002), and the presence of inflammation (P = 0.017) were more characteristic of VS fibrosarcomas than of NVS fibrosarcomas. The study showed that in the absence of any vaccination history, the age of a cat, coupled with certain histological characteristics (e.g., tumour location in skin, and inflammation), may help in distinguishing VS fibrosarcomas from NVS fibrosarcomas. The characteristic histological features of VS fibrosarcomas, such as necrosis, increased mitotic activity and pleomorphism, are those of aggressive tumours.

Age Factors↗

The detection of Tel-TrkC chimeric transcripts is more specific than TrkC immunoreactivity for the diagnosis of congenital fibrosarcoma.

The t(12;15)(p13;q25) translocation, a recurrent chromosomal abnormality of congenital fibrosarcoma, leads to the expression of a Tel-TrkC fusion transcript. To determine whether detection of the chimeric protein may be helpful for the diagnosis of congenital fibrosarcoma, immunohistochemistry was performed with an anti-TrkC antibody on 26 spindle cell tumours of newborn or young children (n=19) or adults (n=7). Four out of five congenital fibrosarcomas showed TrkC immunoreactivity with cytoplasmic paranuclear staining. However, TrkC immunoreactivity was not restricted to congenital fibrosarcoma and was observed in infantile myofibromatosis, congenital haemangiopericytoma, desmoid tumour, nodular fasciitis, fibrous hamartoma, inflammatory myofibroblastic tumour, and adult fibrosarcoma. RT-PCR analysis was performed on nine cases, including four congenital fibrosarcomas, for which frozen material was available. Tel-TrkC transcripts were detected by RT-PCR in the four congenital fibrosarcomas analysed, but not in the five other spindle cell tumours. Furthermore, several Tel-TrkC transcripts encoding for kinase isoforms of the Tel-TrkC protein were detected in congenital fibrosarcoma and may be involved in oncogenesis. The reciprocal TrkC-Tel transcript was detected in only one congenital fibrosarcoma. While the detection of a Tel-TrkC fusion transcript is a recurrent feature of congenital fibrosarcoma, TrkC immunoreactivity does not appear specific for the diagnosis of fibromatous paediatric tumours.

Adult↗

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↗