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[Fibrosarcoma of the larynx].

Fibrosarcoma is the most common neoplasm of the larynx of mesenchymal origin. Between 1991 and 1996 three cases of fibrosarcoma were observed in the ENT Clinic of the Pomeranian Medical Academy. There were two males and one female aged 49-66. It makes 0.5% (3 in 655 cases) of all malignant neoplasms of the larynx treated by surgery in the mentioned period of time. The primary focus of the neoplasm in one case was located in anterior commissure and in the two others--in the vocal cord. In all the cases surgery was done. Results of the treatment were given.

Aged↗

Adoptive immunotherapy of a Gross virus producing lymphoma and a methylcholanthrene-induced fibrosarcoma in tolerant rats.

Immunological tolerance to Gross virus-specific transplantation antigens in rats given neonatae transfer of donor lymphoid cells beneath the kidney capsule of syngeneic recipient rats. Immune or normal donor cells invariably developed a cell-mediated immune reaction in kidneys of GV-tolerant recipients, presumably against GV antigens present on the surface of recipient lymphoid cells in the kidney. Spleen and lymph node cells from tolerant rats failed to develop a reaction in tolerant recipients, but developed a strong reaction to histoincompatible antigens in the kidneys of semisyngeneic tolerant rats. The immunologically tolerant state in the rats could be broken by adoptive transfer of spleen and lymph node cells from syngeneic rats immunized with GV-induced lymphoma cells. Immunotherapy of a GV-induced and also a GV-infected methylcholanthrene-induced fibrosarcoma growing in tolerant rats was successful when immune spleen and lymph node cells were administered i.p. 3 days after s.c. inoculation of 2 X 10(7) tumor cells in the case of the lymphoma, and 1 day after inoculation of 5 X 10(6) tumor cells in the case of the fibrosarcoma.

AKR murine leukemia virus↗

Direct correlation between nitric oxide synthase II inducibility and metastatic ability of UV-2237 murine fibrosarcoma cells carrying mutant p53.

The relationship between nitric oxide synthase II (NOS II) inducibility and the metastatic ability of UV-2237 murine fibrosarcoma cells was determined. Highly metastatic cells survived to produce numerous lung metastases after i.v. injection in syngeneic C3H/HeN mice, whereas poorly metastatic cells did not. Highly metastatic clones exhibited higher levels of NOS II than did poorly metastatic clones in response to interleukin 1alpha and IFN-gamma stimulation. Furthermore, both poorly and highly metastatic clones contained an identical p53 mutation. Overexpression of NOS II in a highly metastatic clone by transfection with NOS II gene retarded tumor growth and completely suppressed metastasis. Our data indicate that a low to moderate level of NOS II expression directly correlates with metastatic ability of UV-2237 fibrosarcoma cells carrying mutant p53 and that a high level of nitric oxide production suppresses tumor growth and metastasis.

Animals↗

[Cardiac fibrosarcoma discovered by cerebral metastases].

Primary heart tumors are rare, and the fibrosarcomas are exceptional. We present the findings in a 78 year old female who has been hospitalized in April 1997 with a history of 4 months of malaise, headaches and weight loss. Clinical examination showed a right lateral homonymous hemi-anopsia. Computed tomography (CT-Scan) of the brain showed two lesions in the occipital and temporal lobe, consistent with metastasis. Thoracic and abdominal-pelvic CT-Scan revealed a voluminous mass of the left auricle that has been interpreted as a probable sarcoma. Biopsy specimen of one of the cerebral lesions, performed at the Centre hospitalier universitaire vaudois (CHUV) on April 29th 1997, revealed fragments of a poorly differentiated sarcoma. After referral back to Neuchâtel, the patient suffered suddenly three weeks later from a cerebral vascular insult with instant onset of deep coma. She deceased on May 27. At autopsy we found a neoplastic lesion of the left auricle with invasion of the pulmonary veins. The histological appearance is similar to the appearance of the cerebral metastasis, showing a proliferation of spindled cells with a partial positivity for Vimentine. It was classified as a fibrosarcoma. Metastasis were found only in the brain with postoperative ischemic left occipitotemporal necrosis and neoplastic emboli.--We are discussing the various incidences of cardiac neoplasms in autopsies or biopsies.

Aged↗

Glucocorticoid receptor-induced down-regulation of MMP-9 by ginseng components, PD and PT contributes to inhibition of the invasive capacity of HT1080 human fibrosarcoma cells.

We examined the effects of the purified ginseng components, panaxadiol (PD) and panaxatriol (PT), on the expression of matrix metalloproteinase-9 (MMP-9) in highly metastatic HT1080 human fibrosarcoma cell line. A significant down-regulation of MMP-9 by PD and PT was detected by Northern blot analysis. However, the expression of MMP-2 was not changed by treatment with PD and PT. Quantitative gelatin based zymography confirmed a markedly reduced expression of MMP-9, but not MMP-2 in the treatment of PD and PT. To investigate whether the reduced level of MMP-9 by PD and PT affects the invasive capacity of HT1080 cells, we conducted an in vitro invasion assay with PD and PT treated cells. The results of the in vitro invasion assay revealed that PD and PT reduced tumor cell invasion through a reconstituted basement membrane in the transwell chamber. Because of the similarity of chemical structure between PD, PT and dexamethasone (Dexa), a synthetic glucocorticoid, we investigated whether the down-regulation of MMP-9 by PD and PT were mediated by the nuclear translocation of glucocorticoid receptor (GR). Increased GR in the nucleus of HT1080 human fibrosarcoma cells treated by PD and PT was detected by immunocytochemistry. Western blot and gel retardation assays confirmed the increase of GR in the nucleus after treatment with PD and PT. These results suggest that GR-induced down-regulation of MMP-9 by PD and PT contributes to reduce the invasive capacity of HT1080 cells.

Cell Nucleus↗

Multiple diffuse fibrosarcoma of bone.

Multiple diffuse fibrosarcoma of bone is a very rare condition, with only 3 cases reported. Its presentation is like that of a multiple myeloma or a metastatic tumor, with multiple osteolytic lesions, and its extent is limited to the bones. Disseminated involvement of the vertebrae was detected in a 26-year-old man, suggesting a metastatic tumor; however, no primary organ or soft-tissue mass was identified. The histopathologic findings of the biopsy material were consistent with fibrosarcoma. Despite treatment, the patient died within 15 months.

Adult↗

Overexpression of manganese superoxide dismutase gene suppresses spontaneous apoptosis without a resultant alteration in in vivo growth of the mouse fibrosarcoma, FSa-II.

The relationship between spontaneous apoptosis and overexpression of manganese superoxide dismutase (MnSOD) gene was examined in vivo. The mouse fibrosarcoma cells expressing high MnSOD activities due to transfection with the human MnSOD cDNA (SOD-H), or the fibrosarcoma cells transfected with the selectable marker alone (NEO), were transplanted into immune-deficient Fox Chase SCID C.B-17/Icr-scid Jcl mice. Apoptosis in tumors was visually quantified by the in situ end-labeling method. The number of apoptotic cells in the SOD-H tumors was significantly less than that in the NEO tumors. The tumor growth time of the SOD-H tumors to grow from 34 to 500 mm3 in one-half of the mice was slightly longer than that of the NEO tumors, but the difference was not statistically significant. These results suggest that overexpression of MnSOD gene is involved in the suppression of spontaneous apoptosis, without a resultant alteration in the tumor growth.

Animals↗

A rare case of fibrosarcoma of the inferior vena cava expanding into the right atrium.

The authors report in detail a case of fibrosarcoma of the inferior vena cava. A 53-year-old female presented with echographic and computed tomographic evidence of a solid formation in the porta hepatis that fused with the inferior vena cava. Because of appearance and rapid development of symptoms of right cardiac failure, the patient was transferred to the Clinic of Cardiac Surgery and underwent an emergency operation. A solid formation arising from the inferior vena cava and expanding into the right atrium was found during the operation. The operation performed was not a radical one. Fibrosarcoma of the inferior vena cava was proved on histological examination. A single therapeutic course with vincristine and farmorubicin was administered. The patient died from recurrence of the malignancy 26 months after the operation. The epidemiologic, diagnostic, and therapeutic aspects of the case are discussed in relation with the literature data.

Echocardiography↗

Primary fibrosarcoma of bone. Outcome after primary surgical treatment.

To investigate outcome and evaluate prognostic factors in primary fibrosarcoma of bone, all patients at the authors' institution who had surgical treatment for primary fibrosarcoma of bone from 1910 to 1995 were studied. Medical records, surgical reports, radiographs, and histologic slides of 92 patients (51 males, 41 females; mean age, 38 years; range, 8-84 years) were reviewed. The most common tumor locations were the femur (28 patients), tibia (21 patients), and pelvis (14 patients). Sixty-one tumors (66%) were Enneking Stage IIB. Twenty-nine patients (31.5%) had adjuvant therapy: 16 had radiation, nine had chemotherapy alone, and four had radiation and chemotherapy. Amputation or disarticulation was performed in 61 patients (66%), wide excision was performed in 13 (14%), marginal excision was performed in 15 (16%), and intralesional excision was performed in three (3.3%). Local recurrence occurred in 14 patients (15%) at a median time of 7 months (range, 3-21 months). Metastases developed in 58 of the 85 patients (68%) with Stage I or II tumors at presentation, at a median of 9 months (range, 1-51 months). Survivorship analysis showed that the overall probability of survival was 33.4% at 5 years after surgery. Multivariate analysis showed that the main prognostic risk factors affecting overall survival included age older than 40 years, tumor location in the axial skeleton, and high-grade tumor (Grade 3 or 4). With the high incidence of systemic failure after surgical treatment, perioperative adjuvant treatment modalities should be considered.

Adolescent↗

Stanniocalcin 1 and 2 are secreted as phosphoproteins from human fibrosarcoma cells.

Stanniocalcin 1 (STC1) and stanniocalcin 2 (STC2) are two recently identified mammalian peptide hormones. STC1 plays a role in calcium and phosphate homoeostasis, while the role of STC2 is unknown. We examined a human fibrosarcoma cell line, HT1080, that has high steady-state STC1 and STC2 mRNA levels, to determine whether these proteins are secreted. Following incubation of HT1080 cells with (32)P, labelled STC1 and STC2 were found to be secreted into the medium. STC1 was phosphorylated in vitro by protein kinase C (PKC). In vitro and in vivo phosphorylation both occurred exclusively on serine and the phosphopeptide maps were similar, suggesting that PKC might be the in vivo kinase. STC2 was phosphorylated in vitro by casein kinase II (CK2), in vitro and in vivo phosphorylation were exclusively on serine and the phosphopeptide maps were indistinguishable. Phosphorylation of STC2 in intact cells resulted from the action of an ecto-protein kinase, since exogenous STC2 was phosphorylated by HT1080 cells and no phosphorylated STC2 was detectable inside the cells. The ectokinase activity was abolished by heparin and GTP could substitute for ATP as the phosphate donor, indicative of an ecto-CK2-like activity. The in vitro CK2 phosphorylation site was shown by matrix-assisted laser-desorption ionization-time-of-flight MS to be a single serine located between Ser-285 and Ser-298 in the C-terminal region of STC2. This is the first report of the secretion of STC1 or STC2 from mammalian cells. We conclude that these human fibrosarcoma cells express both STC1 and STC2 as secreted phosphoproteins in vivo, with STC2 being phosphorylated by an ecto-CK2-like enzyme.

Blotting, Western↗

[Effect of carrageenan and indomethacin on the growth of a murine fibrosarcoma].

In order to grow, solid tumors need to develop new blood vessels. Neoplastic cells secrete growth factors that stimulate angiogenesis and tumor growth. Since Carrageenan acts as in vitro blocking agent which interferes with growth factor-receptor binding, we tested its action in vivo in order to analyze its growth inhibition capability in an experimental murine fibrosarcoma model. Indomethacin was used as a non-steroidal anti-inflammatory agent to neutralize the inflammatory action of Carrageenan. A murine fibrosarcoma was induced with methylcholanthrene in Balb/c mice and maintained by serial passage of tumor cells in mice of the same strain. Tumor volume was evaluated measuring two dimensions and applying the formula V = 0.4 x d2 x D. The mice with tumors were separated into groups; one of them was used as control and the other ones were treated with Indomethacin, Carrageenan and Carrageenan-Indomethacin. Tumor volume was compared between groups using the Student t Test. We demonstrated that Carrageenan and Indomethacin inhibit tumor growth. The inhibitory action of Carrageenan is significantly higher than the antitumoral effect of either Indomethacin or Carrageenan-Indomethacin.

Animals↗

Congenital infantile fibrosarcoma of the upper extremity.

Congenital-infantile fibrosarcoma is an unusual childhood tumor that occurs mainly in children under 5 years of age. More than 300 cases have been reported in the literature so far, very few of them at birth. A distinction must be made between it and its adult counterpart because of differences in their clinical behaviour. We report here a case of congenital fibrosarcoma in a 4-day-old female infant.

Female↗

Measurement of CD2 expression levels of IFN-alpha-treated fibrosarcomas using cell tracking velocimetry.

METHODS: A methodology and a mathematical relationship have been developed that allow quantitation of the expression levels of cellular surface antigens, in terms of antibody binding capacities (ABC). This methodology uses immunomagnetically labeled cells and calibration microbeads combined with cell tracking velocimetry (CTV) technology to measure magnetophoretic mobilities corresponding to cellular ABC. The mobility measurements were accomplished by microscopically recording and calculating the velocity of immunomagnetically labeled QSC microbeads and cells in a nearly constant magnetic energy gradient. RESULTS: Transformed fibrosarcoma cells were given controlled treatments of interferon-alpha in order to manipulate CD2 antigen expression levels. These cells were then immunomagnetically labeled with anti-CD2 FITC antibodies and anti-FITC MACS paramagnetic nanoparticles. Measured magnetophoretic mobilities were used to calculate ABC for these cells, corresponding to CD2 expression levels. CONCLUSION: The results from CTV and flow cytometry (FCM) qualitatively verify that these fibrosarcoma cells express elevated levels of CD2 molecules with increasing interferon-alpha treatment from 0 to 24 h. The mean basal CD2 expression level, in terms of ABC, was calculated to be 27,000 from CTV analysis, whereas FCM indicates a comparable ABC value of 33,000.

CD2 Antigens↗

[Infantile fibrosarcoma: a clinicopathological and molecular study of five cases].

We report 5 cases of infantile fibrosarcoma (4 boys and 1 girl) whose average age was 5, 7 months (range 0 days to 14 months). The tumor was congenital in 4 cases. All tumors presented in the extremities (forearm, hand, thigh: 1 case, lower leg: 2 cases). Treatment was based on surgery (3 cases: amputation, 2 cases: local excision) with a favorable course in all cases, even those with marginal excision (follow-up ranging from 5 to 21 years). The lesions were characterized by dense monotonous cells growing in a fascicular pattern, with small necrotic areas and scattered lymphocytes. The mitotic index was high (average 8/10 high-power fields). ETV6-NK3 chimeric RNA was detected by reverse transcriptase polymerase chain reaction in two cases out four cases from paraffin-embedded tissue blocks. The infantile fibrosarcoma is a good prognosis tumor characterized by particular histological features and ETV6-NK3 gene fusion.

Female↗

Preliminary evaluation of mast cells and angiogenesis processes in experimental fibrosarcoma.

The aim of the study was the evaluation of angiogenesis processes in fibrosarcoma induced by 3-methylcholanthrene (3-Mc) in reference to the number of mast cells (MCs). 76 male Wistar rats were divided into 4 groups: two experimental (E) groups--after injection of 0.2 mg 3-Mc dissolved in olive oil (0.25ml), and 2 control (C) groups. In E1 group, 52 rats were killed after development of the fibrosarcoma; E(2)--10 rats were killed before development of the tumor; C(1)-8 rats received 0.25ml olive oil; C(2)--8 rats received no treatment. Tissue material was fixed in buffered formalin or Carnoy's and Bouin's fluid. Paraffin sections were stained with H+E and Azan methods, and with alcian blue-saphranine and toluidine blue. Immunohistochemical reactions detecting tryptase in MCs were also performed. Angiogenic objects (microvessels and single endothelial cells) were recognized using antibodies against factor VIII (vWF), P selectin (CD-62P), and CD-90. We found a distinct relationship between intensification of neoangiogenesis at the tumor periphery and increased number of MCs.

Animals↗

[Peripheral ameloblastic fibrosarcoma].

We describe the clinicopathological features of a peripheral ameloblastic fibrosarcoma (PAFS) diagnosed in a 89-years-old man with a past history of recurrent peripheral ameloblastoma. Like other peripheral odontogenic tumors, PAFS shows histological features comparable to those of the central intraosseous form, with (fibro)sarcomatous proliferation associated to benign-appearing ameloblastomatous areas. The differential diagnosis must be made with a low-grade spindle ameloblastic carcinoma and with a collision tumor (a non odontogenic sarcoma associated with a recurrent ameloblastoma). Almost any odontogenic tumor has been observed in the peripheral soft tissues, but our case seems to be, to our best knowledge, the first case of PAFS reported in the literature. This fact can only reflect the rarity of its central counterpart. A particular feature is the old age of our patient (ameloblastic fibrosarcoma usually occurs in adolescent or young adult). Another particular feature is that this PAFS appeared in the contiguity of a recurrent peripheral ameloblastoma. As proposed by many authors, this finding suggests that peripheral odontogenic tumors should require a long-term follow-up and, maybe, a more aggressive initial surgical management.

Aged↗

CVMP advice on injection-site fibrosarcomas in cats.

In response to increasing concern, the Committee for Veterinary Medicinal Products (CVMP) has produced this advisory notice for veterinary surgeons on the development in cats of fibrosarcomas at sites of administration of veterinary medicinal products. The advice relates principally, but not exclusively, to the subcutaneous injection of vaccines. The issue is of relevance only to cats and no extrapolation should be made to other species or to man. At the current state of knowledge, it is not possible to provide specific advice on the risk that any product, or any type of product, might represent in terms of inducing a fibrosarcoma at the site of administration. However, following the precautionary principle, the CVMP considers that information on this issue should be made available to veterinary surgeons in order that they can have an informed discussion with owners of the benefits and risks of therapeutic interventions in cats, particularly in relation to vaccination and re-vaccination. The CVMP wishes to emphasise that modern vaccines continue to represent the only safe and effective means of protecting cats against serious infectious diseases and this should be taken fully into account in any discussion between veterinary surgeons and owners of cats.

Animals↗

Release of transforming growth factor-beta 1 from the pericellular matrix of cultured fibroblasts and fibrosarcoma cells by plasmin and thrombin.

A sensitive immunoblotting assay was developed for the detection of transforming growth factor (TGF)-beta 1 from cell extracts and culture medium. HT-1080 human fibrosarcoma cells and human fibroblasts were used as models for the secretion and proteolytic release of pericellular matrix-associated TGF-beta 1. Analysis of the pericellular matrices of the cells indicated that the majority of cell-layer associated TGF-beta 1 was associated with the pericellular matrix. Treatment of the cells with plasmin or thrombin released the matrix-associated TGF-beta 1 to the culture medium. Assays for the biological activity of plasmin-released TGF-beta 1 by Mv1Lu cell growth inhibition assays indicated that the majority was in the latent form. Northern hybridization analyses indicated that the mRNA levels of TGF-beta 1 were not elevated during the proteinase treatment. Experiments using radiolabeled TGF-beta 1 indicated that exogenous active TGF-beta 1 associates mainly with the presumed TGF-beta 1 receptors that were not retained in the extracellular matrix preparations. These results indicate that a major fraction of latent TGF-beta 1 that is produced by the cells is deposited to and remains associated with the pericellular matrices of cultured fibroblasts and fibrosarcoma cells, and that matrix-associated TGF-beta 1 is very susceptible to release by various proteolytic enzymes.

Animals↗