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Effect of the cytokine rhTNF-alpha on the population of mast cells in the growth of MethA fibrosarcoma--a TEM study.

The aim of the present study was the ultrastructural characteristics of mast cell (MC) involved in host antitumor responses induced by local (i.t.) administration of recombinant human tumor necrosis factor alpha (rhTNF-alpha) in the primary focus of methA fibrosarcoma. MC were involved in tumor interstitium remodeling. Numerous mitochondria, well-developed RER and Golgi apparatus, clusters of polyribosomes, considerable polymorphism of granules and differentiated lamellar structures which frequently presented myelinic forms were observed after rhTNF-alpha application. In the study numerous fibres of the fibrous tissue, richly vascularized, occurred in the peripheral and intermediate tumor zones. Cluster of MC and tumor cells were seen on the border of the necrotic foci. However, proteolytic enzymes released by MC cause interstitial lysis, ensuring the place for tumor growth, and are involved in angiogenesis. Thus, it is not clear whether MC contribute to the inhibition of tumor growth or have an adjunctive role in tumor progression.

Animals↗

Preliminary evaluation of mast cells in rats with an experimental fibrosarcoma induced by 3-methylcholanthrene.

The aim of the study was the evaluation of mast cells in experimental fibrosarcoma induced in the rats' skin. Experiments were carried out on 50 male Wistar rats divided into three groups: 1. The cancer was induced in 34 rats' by onefold subcutaneous injection of 0.2 mg 3-methylcholanthrene in 0. 25 ml of olive oil; 2.--8 rats received subcutaneous injection of 0.25 ml olive oil; and 3.--8 rats, no treatment. The tumors developed after 14-35 weeks. The examined tumors had the mass of 1 g to 176 g--mean 15 g. Tissue material was fixed in Carnoy's or Bouin's fluid. Paraffin sections were stained with hematoxylin and eosin and using Azan methods. Mast cells were stained with alcjan blue+saphranin and with toluidine blue in pH 1.5. Immunohistochemical reactions detecting tryptase in mast cells and von Willebrand Factor in endothelial cells were also performed--using specific antibodies (DAKO) and ABC complex. We have found a very significant growth of the quantity of mast cells in the connective tissue of tumours. The distinct increase in immunostaining was found for tryptase in mast cells of the tumor periphery zone, where most areas of strong neoangiogenesis were found.

Animals↗

Inhibition of activator protein-1 binding activity and phosphatidylinositol 3-kinase pathway by nobiletin, a polymethoxy flavonoid, results in augmentation of tissue inhibitor of metalloproteinases-1 production and suppression of production of matrix metalloproteinases-1 and -9 in human fibrosarcoma HT-1080 cells.

Medicinal plants contain pharmacological substances including flavonoids, and their extracts have been therapeutically administered for cancer therapy in vitro and in vivo. We investigated the efficacy of a polymethoxy flavonoid, nobiletin, from Citrus depressa on tumor invasion in vitro. Nobiletin inhibited the tumor-invasive activity of human fibrosarcoma HT-1080 cells in the Matrigel model, whereas a similar inhibition was observed upon exogenously adding tissue inhibitors of metalloproteinases (TIMPs)-1 and -2. The gene expression and production of pro-matrix metalloproteinase 9 (proMMP-9)/progelatinase B and proMMP-1/interstitial procollagenase were specifically suppressed by nobiletin in 12-O-tetradecanoylphorbol 13-acetate-stimulated HT-1080 cells. In contrast, the gene expression and production of TIMP-1, but not TIMP-2, were enhanced by nobiletin. We also demonstrated that nobiletin suppressed the 12-O-tetradecanoylphorbol 13-acetate-induced binding activity of activator protein-1. Furthermore, a phosphatidylinositol 3-kinase inhibitor, LY-294002, was found to mimic the different actions of nobiletin on the production of proMMP-9 and TIMP-1. These results suggest that nobiletin inhibits tumor cell invasive activity not only by suppressing the expression of MMPs but also augmenting TIMP-1 production in tumor cells, and that the nobiletin-mediated inhibition of activator protein-1 binding activity is at least partly involved in the suppression of MMP expression. Furthermore, we suggest a possible mechanism by which nobiletin may interfere in the phosphatidylinositol 3-kinase pathway, which divergently regulates the production of MMP and TIMP-1.

Anticarcinogenic Agents↗

Cytogenetic, cytological, and virological characteristics of a bovine fibrosarcoma.

The features of a bovine tumor with typical histopathological characteristics of a malignant fibrosarcoma are described. Direct karyotype preparations from the tumor tissue showed two populations of cells with bizarre karyotypes. An in vitro cell culture, designated BS-2, derived from the tumor had a normal diploid karyotype. This culture formed syncytia and produced a virus morphologically indistinguishable from the ubiquitous bovine syncytial virus. BS-2 cells reacted strongly in immunofluorescent tests with both bovine syncytial virus reference serum and serum from the tumorous cow. The virus was also demonstrated by immunofluorescence and mixed culture techniques in the buffy coat cells of the same cow.

Animals↗

Clinicopathologic features, diagnosis, and treatment of fibrosarcoma of bone.

Fibrosarcoma of bone is a relatively rare tumor; it accounts for less than 5% of bone sarcomas. The anatomical sites most commonly involved are the metaphyses of long tubular bones. Local pain, swelling, limitation of motion, and pathologic fracture are the common clinical signs and symptoms. Typical imaging findings include eccentrically located lytic lesions, with a geographic, moth-eaten, or permeative pattern of bone destruction, and extension into adjacent soft tissues. Surgery is the treatment of choice. The type of surgical procedure depends mainly on histologic grade, local conditions, and tumor location. With a high probability of metastases (>70%) after surgical treatment, perioperative adjuvant treatment modalities should be considered for high-grade tumors. The most important prognostic factors affecting survival include tumor grade, patient's age, and tumor location.

Bone Neoplasms↗

Fibrosarcoma of the sacrum in a child: management by sacral resection and reconstruction.

We describe the diagnosis and surgical management of fibrosarcoma of the sacrum in a pediatric patient. We retrospectively reviewed the literature and a case report. Total sacrectomy is a viable treatment option in the management of large malignant sacral tumors. The techniques used in adult patients can be extended to and improved upon for pediatric patients. The input of multiple surgical specialties is essential in the management of these lesions.

Bone Neoplasms↗

[Ameloblastic fibrosarcoma: an immunohistochemical and ultrastructural study of the mesenchymal component].

To study the characteristics of the mesenchymal cells of ameloblastic fibrosarcoma (AFS), three cases of AFS were studied immunohistochemically and ultrastructurally. The results showed that the mesenchymal component of AFS consisted predominantly of fibroblastic cells with a small number of undifferentiated cells, a few histiocytes and occasionally myofibroblastic cells under electron microscope. The fibroblastic cells were Vimentin positive only, and myofibroblastic cells were positive for Vimentin, HHF35 and alpha-SMA. The histiocytes were positive both for kp1 and PG-M1, suggesting that these cells were infiltrating cells from peripheral blood rather than histiocytic differentiation of tumor cells. Compared with ameloblastic fibroma, AFS showed much higher PCNA labeling index, suggesting higher proliferation activity of AFS.

Fibrosarcoma↗

Hematopoiesis-stimulating and anti-tumor effects of repeated administration of diclofenac in mice with transplanted fibrosarcoma cells.

Positive effects of repeated administration of diclofenac, an inhibitor of prostaglandin synthesis, in terms of prevention of tumor development and stimulation of hematopoiesis have been observed in C3H mice transplanted subcutaneously with G:5:113 fibrosarcoma cells. Fourteen-day treatment with diclofenac (3.75 microg/kg/day) started from day 5 after tumor cell transplantation. Measurements of tumors and hematological examinations were performed on day 30. The results strongly suggest the possibility that inhibitors of prostaglandin synthesis (non-steroidal anti-inflammatory drugs) may be used in oncological practice where the observed effects are highly desirable.

Animals↗

A novel matrix metalloproteinase inhibitor, FYK-1388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line.

The matrix metalloproteinases (MMPs) are likely to contribute to tumor cell invasion, metastasis and angiogenesis. Several MMP inhibitors have been developed, recently and their anti-tumor efficacy is being evaluated in clinical trials. FYK-1388 is a novel broad MMP inhibitor which blocks the activity of MMP-1, -2, -3, -7, -9, -13 and -14 (MT-MMP-1). It is especially effective against MMP-2 and -9 more so than other MMP inhibitors such as Marimastat, Ro 32-3555 and D-2163. Here, we investigated the anti-tumor efficacy of FYK-1388 using the human fibrosarcoma cell line HT-1080. These cells produced MMP-2 and -9, which FYK-1388 inhibited at a dose of 10(-8) M. FYK-1388 at 0.2 mg/mouse/day significantly suppressed tumor growth when given by s.c. injection for 22 days, experimental lung metastasis after 5 days s.c. injection and also suppressed tumor-induced angiogenesis in the dorsal air sac assay after 7 days s.c. injection. In the MTT assay, FYK-1388 had no effect on the in vitro growth of HT-1080 cells. These results suggest that FYK-1388 possesses anti-tumor efficacy as a result of inhibiting angiogenesis through the suppression of MMP-2 and -9 activity.

Angiogenesis Inhibitors↗

Effect of Corynebacterium parvum on the response to irradiation of a C3H fibrosarcoma.

A methylcholanthrene-induced fibrosarcoma of C3H mice has been used as 5th- to 6th-generation syngeneic transplant in an investigation of the role of Corynebacterium parvum as an adjuvant to the therapeutic effect of local irradiation of established tumors. The most effective route for administration of C. parvum in this tumor system was i.v., and the greatest effect of the C. parvum-mediated tumor graft rejection was observed for tumor growing intracutaneously or s.c. An intermediate level of effectiveness was obtained for tumor growing i.m. The combined C. parvum and local irradiation studies were performed using tumors growing in the leg muscle and measuring 8 mm in diameter at the time of local irradiation. Several routes of administration of C. parvum, dose levels of C. parvum, and time relationships between administration of C. parvum and irradiation were investigated. The outstanding finding was that very low doses of radiation were quite effective when administered to tumors growing in animals pretreated with C. parvum. This was true for radiation administered as a single or fractionated dose (10 equal doses spread over 18 days). For single-dose irradiation the effect was relatively dose independent over the range of 200 to 3000 rads. Some indication was obtained that local irradiation may impair the tumor graft rejection reaction. No evidence was obtained of an enhanced growth of tumor. Regression of tumor following irradiation was not modified by pretreatment with C. parvum. The mice that were unsuccessfully treated by radiation and C. parvum had a lower incidence of metastatic disease in the lung than did the mice treated unsuccessfully with radiation alone.

Adjuvants, Immunologic↗

Photodynamic therapy with verteporfin in the radiation-induced fibrosarcoma-1 tumor causes enhanced radiation sensitivity.

Photodynamic therapy (PDT) with verteporfin (lipid form of benzoporphyrin derivative,benzoporphyrin derivative monoacid ring A) was used to treat radiation-induced fibrosarcoma tumors before X-ray treatment. When verteporfin was injected 3 h before light irradiation, the tumor partial pressure of oxygen (pO(2)) rose from a pretreatment value of 2.8 +/- 1 to 15.2 +/- 6.9 mm Hg immediately after light application was complete (P = 0.048). When the optical irradiation was given 15 min after verteporfin injection, the tumor pO(2) decreased slightly after treatment [i.e., 6.8 +/- 1.6 mm Hg (pretreatment) versus 4.1 +/- 0.3 mm Hg (posttreatment)], whereas control tumor pO(2) did not change significantly. In vitro study of the cellular oxygen consumption rate before and after PDT treatment indicated that the consumption rate decreased linearly with delivered optical dose and quantitatively matched the loss of cell viability as measured by a mitochondrial tetrazolium assay. Doppler measurements show that red cell flux is still patent immediately after treatment, indicating that oxygen should still be delivered to the tumor. Computational simulations of the oxygen supply from the vessels and the consumption from mitochondrial activity confirmed that if oxygen consumption is decreased in the presence of unhindered blood flow, the tumor oxygenation should rise, and the hypoxic fraction of the tumor should decrease. Combination treatments with PDT delivered (100 J/cm(2) optical dose, with 1 mg/kg benzoporphyrin derivative monoacid ring A injected 3 h before treatment) after radiation treatment (10 Gy from 300 keV source) were compared with PDT delivered simultaneously with radiation. Tumor regrowth assay showed that the delays to reach double the tumor volume for PDT alone and radiation alone were 2.7 +/- 1.6 and 3.2 +/- 1.7 days, respectively. When radiation was given before PDT, the delay was 5.4 +/- 1.4 days, and when PDT was given at the same time as radiation, the delay was 8.1 +/- 1.5 days. This observation indicates that the combined effect in the latter case was greater than additive (P = 0.049).

Animals↗

Activation of the lymphotoxin-beta receptor induces NFkappaB-dependent interleukin-6 and MIP-2 secretion in mouse fibrosarcoma cells.

Activation of the lymphotoxin beta-receptor (LTbetaR), a member of the tumor necrosis factor receptor family, plays a crucial role in lymphoid organogenesis and tumor development. Lymphotoxin alpha(1)beta(2) (LTalpha(1)beta(2)) and LIGHT have been identified as membrane anchored ligands for the LTbetaR. While LTbetaR is expressed on a wide range of cell types e.g. fibroblasts and monocytes, the ligands are expressed only on activated lymphocytes and NK cells. In order to characterize LTbetaR expression and the biological consequences of LTbetaR activation rat anti-mouse LTbetaR monoclonal antibodies were generated. These antibodies recognized a mouse LTbetaR-Ig fusion protein as well as endogenous LTbetaR on a variety of mouse fibroblast and fibrosarcoma cell lines. Specificity was demonstrated by the lack of binding to LTbetaR-deficient embryonic fibroblasts. Competitive binding studies revealed that three different epitopes were recognized by the monoclonal antibodies. Two of the monoclonals activated the LTbetaR and induced activation of NFkappaB and secretion of MIP-2 and IL-6 in L929 mouse fibroblast cells. MIP-2 and IL-6 secretion was NFkappaB-dependent because IkappaB-transfected cells released significantly reduced amounts of both mediators.

Animals↗

Differential expression of the H-2Dk MHC class-I antigen and tissue inhibitor of metalloproteinases in metastatic and nonmetastatic T-10 fibrosarcoma cells.

In previous studies, we have demonstrated that the highly metastatic IE-7 cell clone, derived from the T-10 fibrosarcoma, expressed both the H-2Dk and H-2Db genes, whereas a nonmetastatic IC-9 clone, derived from the same tumor, expressed only H-2Db, suggesting that the H-2Dk product might be involved in the metastatic phenotype. To substantiate this notion, IC-9 cells were transfected with an H-2Dk-expressing vector. Although all of the 4 randomly selected transfectant subclones elicited high H-2Dk expression, only one was as metastatic as IE-7 cells. This metastatic transfectant resembled IE-7 cells also in its inability to evoke CTL response in syngeneic mice, whereas the other transfectants were quite competent in this respect. It thus appears that the H-2Dk product may contribute to the metastatic phenotype provided that it is immunogenically abnormal. In addition, the present study provides evidence to suggest that lack of production of the tissue inhibitor of metalloproteinases TIMP-1/TIMP-2 is another important determinant in the metastatic phenotype of these cells.

Animals↗

[A comprehensive analysis of osteosarcoma, fibrosarcoma and chondrosarcoma of the jaws].

The clinical, pathological and radiographic materials of 99 cases with osteosarcoma, fibrosarcoma and chondrosarcoma of the jaws were analyzed comprehensively. Neither obvious differences of age, sex, duration, location of tumor, clinical symptoms and five-year survivals nor radiographic characteristics were found between these three types of sarcoma. The tumor stage and destruction of cortical bone by the tumor are the important factors influencing the prognosis of the patients. The radiographic findings are valuable for the estimation of prognosis.

Adolescent↗

Case report of a patient with recurrent fibrosarcoma of the thoracic wall.

A case of a patient with recurrent chest wall fibrosarcoma is presented who had her original tumour removed 12 years earlier. The histology of the primary lesion was missed for a localized fibrous mesothelioma. Author reviews the pathology and management of soft tissue tumours of the thoracic wall.

Aged↗

[Establishment and characterization of human ovarian fibrosarcoma cell line and its sensitivity to anticancer agents].

We succeeded in establishing a cell line (KEN-3) for subculture from a fibrosarcoma which originated in the ovary in a girl aged 17 years. Its characteristics and sensitivity to anticancer agents are reported in this paper. 1. Characteristics of established cell line. Lined cells consist of multinucleated giant cells mixed among many spindle-shaped cells. They grow in small colonies and have none of the pavement-like arrangement characteristic of epithelial tumor cells. The number of chromosomes ranged from 45 to 128 (mode: pseudo-triploidy region, 65). The doubling time, cellular density and plating efficiency were 76.9 hours, 5.4 x 10(5)/cm2 and 30.2%, respectively. Concerning tumor markers, CEA and sialyl SSEA-1 were only produced in small quantities. Subculture was possible subcutaneously in the nude mouse with no capacity for the production of ascites. 2. Susceptibility to anticancer agents and GP170 expression. The in vitro susceptibility to about 12 types of anticancer agents was investigated with the MTT assay. IC50/PPC was shown to be less than 1 for Adriamycin only. The sensitivity to CDDP (IC50/PPC: 4.8) was low, and no sensitivity was observed at all to DTIC, which is used frequently for mesenchymal tumors. GP170 (mdr-1 products) was positive in established cells in immunohistochemical stain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Tumor-specific chemoimmunotherapy of murine fibrosarcoma using tumor-specific transplantation antigen, cyclophosphamide, and interleukin-2.

The anti-tumor effect of active specific chemoimmunotherapy, using butanol-extracted tumor-specific transplantation antigen (TSTA), cyclophosphamide (CY), and continuous intrasplenic infusion of interleukin-2 (IS-IL-2), was assessed in a C3H/HeJ murine methylcholanthrene (MCA)-induced fibrosarcoma model. Sole administration of TSTA induced tumor-specific, suppressor T cells in the spleens of mice bearing 3-day established tumors. Concomitant low-dose (20 mg/kg) CY treatment not only inhibited TSTA-mediated suppressor cell induction, but also evoked splenic lymphocytes of tumor-bearing mice to display tumor-specific cytotoxic activity. High-dose (200 mg/kg) CY abrogated the immunotherapeutic benefit. The immune effectors generated by TSTA plus CY bear the Thy 1, L3T4, Lyt 2 phenotype. Continuous IS-IL-2 infusion in combination with TSTA and CY induced tumor-specific Lyt 2+ cytolytic T cells, as well as the activation of L3T4+ cytostatic T cells. Thus, a triple regimen using TSTA, CY, and IS-IL-2 appears to augment CTL induction in tumor-bearing hosts undergoing stimulation of helper elements by TSTA and inhibition of suppressor cells by CY.

Animals↗