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Enhanced anti-tumour effect of cisplatin with low-voltage electrochemotherapy in hamster oral fibrosarcoma.

The aim of this study was to determine the effects of low-voltage electrochemotherapy with intraperitoneal cisplatin on hamster oral fibrosarcoma. Oral fibrosarcoma was transplanted submucosally into the cheek pouch mucosa of 100 hamsters. After transplantation, the hamsters were randomly divided into four equal groups. These groups received no treatment (D-E-); 2 mg/kg body weight cisplatin treatment without electroporation (D+E-); electroporation without cisplatin treatment (D-E+); or 2 mg/kg body weight cisplatin treatment followed by electroporation (D+E+). Electrical pulse treatment together with cisplatin injection markedly reduced the size of the tumour, whereas cisplatin injection or electrical pulse treatment alone did not. These results clearly indicate that the anti-tumour effect of cisplatin on hamster oral fibrosarcoma was considerably potentiated or enhanced by the administration of local electrical pulses at low voltages.

Animals↗

Primary intraspinal fibrosarcoma.

Fibrosarcomas of dura mater are very rare tumors representing only 0.5% of all central nervous system sarcomas. A higher incidence of dural fibrosarcomas has been reported in patients with neurofibromatosis. We present a case of spinal dura mater fibrosarcoma in a patient without neurofibromatosis. The diagnostic and therapeutic strategy in the clinical management is discussed.

Aged↗

Possible radiation-induced dural fibrosarcoma with an unusually short latent period: case report.

We report a case of radiation-induced dural fibrosarcoma in a 9.5-year-old male patient who was treated with radiation for medulloblastoma. He received a total dose of 53.2-Gy radiation, delivered at 1.6 and 1.8 Gy per fraction with a 6 MV linear accelerator using the standard cranial-spinal technique. A sequential magnetic resonance image at 15 months after the completion of radiation therapy showed a mass above the cerebral convexity that increased two-fold in size within a period of 4 months. The tumor showed characteristics of a low-grade fibrosarcoma. This case emphasizes the potential risk of early development of a second neoplasm after therapeutic radiation, especially in children, and also documents what is to our knowledge the shortest latent period between the administration of radiation therapy and the development of an intracranial fibrosarcoma that has been reported.

Brain Neoplasms↗

Simvastatin, an HMG-CoA reductase inhibitor, reduced the expression of matrix metalloproteinase-9 (Gelatinase B) in osteoblastic cells and HT1080 fibrosarcoma cells.

MMP-9 or Gelatinase B, a member of the matrix metalloproteinase family (MMPs), plays important roles in physiological events such as tissue remodeling and in pathological processes that lead to destructive bone diseases, including osteoarthritis and periodontitis. In addition to its effect on the increase of total bone mass, statin (an HMG-CoA reductase inhibitor) suppresses the expression of MMPs. In this study, we proposed that simvastatin reduces MMP-9 expression in osteoblasts and HT1080 fibrosarcoma cell line. Gelatin zymography, Western blot analysis and reverse transcriptase-PCR were used to investigate the effects of simvastatin on MMP-9 in primary calvaria cells, U2-OS osteosarcoma cells, and HT1080 fibrosarcoma cells. The results from gelatin zymography and Western blot analysis revealed that simvastatin suppressed MMP-9 activity in these cells in concentration- and time-dependent manners. The effective concentrations of simvastatin were 100 - 500 nM, 5 - 15 microM, and 2.5 - 10 microM in primary calvaria, U2-OS, and HT1080 cells, respectively. Collectively, these results suggest that simvastatin is a potent drug for inhibition of MMP-9 expression in osteoblastic cells and HT1080 fibrosarcoma cells.

Animals↗

Feline vaccine-associated fibrosarcoma: morphologic distinctions.

Forty-four primary feline vaccine-associated fibrosarcomas and 16 recurrences were examined histologically for detailed morphologic characterization with emphasis on tumor grade, presence of neoplastic multinucleated giant cells, presence and proportion of T and B lymphocytes within the tumor, and thin and intermediate filament contents of neoplastic and stromal cells. The microvascularity and proliferation rates of central and peripheral areas of the tumors were also quantified by computerized image analysis. For primary fibrosarcomas, 11 of 44 (25%) were grade I, 21 of 44 (47.7%) were grade II, and 12 of 44 (27.3%) were grade III. The recurrences followed a similar pattern: 4 of 16 (25%) were grade I, 8 of 16 (50%) were grade II, and 4 of 16 (25%) were grade III. A positive correlation was found between the presence of neoplastic multinucleated giant cells and tumor grade. These cells were present in 9 of 12 (75%) of grade III and none of the grade I tumors. Prominent peritumoral lymphoid aggregates or follicles were present in 59% of the tumors, and many contained high proportions of T lymphocytes, varying from 19 to 87%. All fibrosarcomas were immunoreactive for vimentin and 28 of 44 (64%) were reactive for alpha-smooth muscle actin. The actin-positive cells were either part of the tumor or formed a capsule around tumor nodules. The peripheral vascularity was significantly higher than the central vascular density but no difference was found in tumor cell proliferation rates between the two areas. Centrally located, fluid-filled micro- or macrocavitations were frequently observed in the large vaccine sarcomas and probably formed secondary to rapid tumor growth and central necrosis.

Animals↗

Fibrosarcoma with typical features of postinjection sarcoma at site of microchip implant in a dog: histologic and immunohistochemical study.

A 9-year-old, male French Bulldog was examined for a subcutaneous mass located at the site of a microchip implant. Cytologic examination of the mass was suggestive of a malignant mesenchymal neoplasm. Histologically, the mass was confirmed as a high-grade infiltrative fibrosarcoma, with multifocal necrosis and peripheral lymphoid aggregates. By immunohistochemistry, the sample was investigated for vimentin, smooth-muscle actin (SMA), CD3, CD79alpha, and CD18. All the neoplastic cells were positive for vimentin. Scattered cells at the periphery of the lesion were also positive for SMA, highlighting a myofibroblastic phenotype. The lymphoid cells were positive for CD18 and CD3. No aluminum deposits were detected by the aurintricarboxylic acid method. A diagnosis of fibrosarcoma morphologically similar to feline postinjection sarcomas was made. Fibrosarcomas at the site of injections have been reported in dogs and ferrets. Furthermore, neoplastic growth at the site of microchip implant in dog and laboratory rodents has been described.

Animal Identification Systems↗

Multiple diffuse fibrosarcoma of bone associated with extramedullary hematopoiesis.

We report a case of multiple diffuse fibrosarcoma of bone. The patient, a 38-year-old man, was referred to our hospital with knee pain, anemia and thrombocytopenia. No solid mass was seen on radiographic examination of the kneejoint, but magnetic resonance imaging showed hypointensity of the distal femur. Femoral biopsy revealed proliferation of long spindle-shaped fibrosarcoma cells, while a bone marrow biopsy of iliac bone (which appeared normal on radiographic examinations) showed replacement of hematopoietic cells by fibroblast-like spindle cells. A diagnosis of multiple diffuse fibrosarcoma of bone was therefore made. Autopsy revealed tumor invasion into multiple bones and several visceral organs and extramedullary hematopoiesis in the liver, spleen and lymph nodes. As this patient had leukoerythroblastic anemia with poikilocytosis, splenomegaly exhibiting extramedullary hematopoiesis, and apparent fibrotic change in his bone marrow, we suggest that this extremely rare disease should be considered in the differential diagnosis of myelofibrosis.

Adult↗

Combined treatment of an intratumoral injection of dendritic cells and systemic chemotherapy (Paclitaxel) for murine fibrosarcoma.

A novel combined treatment of conventional chemotherapy with an intratumoral injection of syngeneic dendritic cells (DCs) has emerged as a potent cancer treatment strategy. In this study, we evaluated the synergistic effect of an intraperitoneal (i.p.) injection of a chemotherapeutic drug, paclitaxel, and an intratumoral (i.t.) injection of syngeneic bone marrow-derived DCs for the treatment of pre-existing fibrosarcoma. Subcutaneous tumors were established using MCA102 fibrosarcoma cells in syngeneic C57BL/6 mice. The results demonstrated that the combined treatment of paclitaxel chemotherapy and the injection of DCs led to complete tumor regression, in contrast to only partial eradication of the tumors with chemotherapy or DCs alone. Furthermore, the tumor-free mice were able to resist a repeat challenge with the same type of tumor. These findings suggest that a combination therapy of systemic chemotherapy along with the intratumoral administration of DCs is a potent treatment strategy for fibrosarcoma.

Animals↗

Effect of administering cyclophosphamide and vitamin E on the levels of tumor-marker enzymes in rats with experimentally induced fibrosarcoma.

Cyclophosphamide, and antineoplastic drug, and vitamin E, the common antioxidant present in the diet, were administered in separate dosages and in combination to animals (rats) with fibrosarcoma, metastatic tumor of the connective tissues, induced. The anticancer drug (20 mg/kg body weight) and the vitamin-E (400 mg/kg body weight) was administered for a period of 28 days from the day of tumor transplantation. The individual and the combined effects of these two substances were investigated by checking the growth of the tumor. Tumor markers like lactate dehydrogenase (LDH), serum glutamate pyruvate transminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), acid phosphatase, and alkaline phosphatase were analyzed for the changes in their concentration in serum, liver, and kidney to assess the success of the therapy. The increased level of the enzymes in the fibrosarcoma-suffering rats (GPII) was reduced by cyclophosphamide treatment (GP III) and vitamin E administration (GP IV). Among the treated groups, the combination therapy (GP V) showed greater efficacy in the treatment of fibrosarcoma than did individual administration, as there was more reduction in the levels of enzymes in Group V than those in to Groups III and IV. The enzyme levels were brought to near the normal level.

Animals↗

E2F-1 has properties of a radiosensitizer and its regulation by cyclin A kinase is required for cell survival of fibrosarcoma cells lacking p53.

Negative regulation of E2F-1 DNA binding function by cyclin A kinase represents part of an S-phase checkpoint control system that, when activated, leads to apoptosis. In this study, we examined the cellular sensitivity and resistance of isogenic mouse fibrosarcoma cell lines, differing primarily in their p53 status, to ectopic expression of wild-type (wt) E2F-1 and cyclin A kinase binding-defective mutants of it. We found that E2F-1 (wt) potently affected the survival of p53+/+ tumor cells but not that of p53-/- cells. In contrast, expression of cyclin A kinase binding-defective E2F-1 species interfered with cell survival of fibrosarcoma cells irrespective of their p53 status. Finally, expression of E2F-1 (wt) in p53-/- fibrosarcoma cells enhanced the cytotoxic effect of ionizing radiation in vitro and in vivo in a mouse tumor model. These results suggest that E2F-1-dependent activation of an S-phase checkpoint is p53 independent and that E2F-1 possesses radiosensitizing properties in the absence of p53.

Animals↗

[Sclerosing epithelioid fibrosarcoma].

Sclerosing epithelioid fibrosarcoma (SEF) was first described in 1995 and since then 39 cases have been reported. Here we describe 6 cases of SEF (3 in women and 3 in men). The patients aged from 22 to 79 years. The tumours were located in soft tissues of the extremities (in 3 cases in the lower, in 2 instances in the upper extremity) and of the trunk (in 1 case). The lesions were partially nodular, of gray-white colour, and hard in consistency. Histologically, they were composed of epithelioid round to ovoid small cells with a sparse cytoplasm and a very low mitotic activity. The tumour cells formed cords and alveoli or were scattered individually within a dense hyalinized collagenous stroma. The neoplasms also contained foci of conventional fibrosarcoma, necrosis, calcification, and metaplastic bone. On immunohistochemistry, the neoplastic cells were positive for vimentin. Two cases were immunoreactive for epithelial membrane antigen and one tumour also for cytokeratins. The proliferative activity, assessed by MIB 1 antibody (Ki-67), was detected in 1-6% of neoplastic cells in primary tumours. Follow-up information was available in 5 patients. In two cases, there were local recurrences and distant metastases (in the lungs, upper extremity, and mediastinum). One of these patients died of SEF. The differential diagnosis of this relatively low-grade fibrosarcoma is broad and includes, along with a variety of benign and malignant soft tissue lesions, infiltrating carcinoma, and, to a lesser extent, sclerosing lymphoma.

Adult↗

Isolation and characterization of a mesenchyme associated antigen from dimethylbenzanthracene induced rat fibrosarcoma.

Using an antiserum directed against human neurospecific antigen and the indirect immunofluorescence technique, we have obtained evidence for the presence of a mesenchyme associated cross-reacting antigen (MAA) in the dimethylbenzanthracene induced fibrosarcoma of the rat. This antigen has been purified from this tumor and compared with the antigen associated with the human nervous system and that associated with the nervous system of the rat. An anti-rat MAA antiserum has been obtained. It has cytotoxic activity against cultured fibrosarcoma cells as measured by release of radioactivity. This antigen can be considered as a marker of fibrosarcomas.

9,10-Dimethyl-1,2-benzanthracene↗

[Congenital fibrosarcoma. Diagnostic-therapeutic implications].

Most of the soft tissue sarcomas of childhood other than rabdomyosarcoma, have as final diagnosis fibrosarcoma, specially in the first months of life. Overlapping features between infantile myofibromatosis and congenital fibrosarcoma, hemangiopericytoma and fibrohistiocytoma have seen noted. Five patients with congenital fibrosarcoma were operated since 1991. Anatomical sites included lower limb, hand and forearm, and three of them had previous diagnoses of hemangiopericytoma, fibrohistiocytoma and myofibromatosis, with provocated non radical surgery and reoperation. The postoperative course was satisfactory and all are live one to eight years later. In our experience accurate histological diagnosis must be achieved to perform radical surgery on these cases.

Fibrosarcoma↗

Lipoxygenase inhibitors suppress proliferation of G5:113 fibrosarcoma cells in vitro but they have no anticancer activity in vivo.

Nordihydroguaiaretic acid (NDGA) and esculetin, both nonspecific inhibitors of lipoxygenases (LOX), were found to suppress expressively the in vitro proliferation of fibrosarcoma cells G5:113 in concentrations ranging from 10 to 50 microM. Subsequent flow-cytometric analysis of the cell cycle showed that both these drugs significantly decreased the percentage proportion of cells in the G0/G1-phase and simultaneously increased significantly this proportion in the S-phase. No apoptosis was detected in the whole range of concentrations studied, from 2.5 to 50 mM. On the contrary, in experiments in vivo, neither NDGA nor esculetin had any curative effect if they were repeatedly injected intraperitoneally (i.p.) into mice bearing tumors growing from subcutaneously (s.c.) transplanted G5:113 cells. Pretreatment of the fibrosarcoma cells with NDGA or esculetin in vitro preceding their s.c. transplantation into mice did not result in suppression of the tumor growth, either. Finally, if G5:113 cells were injected intravenously and the mice were subsequently treated repeatedly with i.p. injections of NDGA, decreased survival and increased number of surface lung metastases were observed in the NDGA-treated group. Thus the suppressive action of inhibitors of LOX on the growth of fibrosarcoma cells in vitro was not reflected in their anti-tumor effects in vivo.

Animals↗

Spontaneous regression of neonatal fibrosarcoma.

We report a case of fibrosarcoma, which presented in a two week old boy. Excision was not performed because it would have required mutilating surgery. The tumour regressed and was impalpable by 7 months of age. The patient is tumour free at 4 years of age. This is the first reported case of spontaneous regression of a fibrosarcoma. The literature is reviewed. We conclude that the chances of metastasis are low, tumours are likely to respond to chemotherapy, and mutilating surgery is not appropriate initial treatment for infantile fibrosarcomas.

Bone Neoplasms↗

Ultrastructural, immunocytochemical, and cytogenetic characterization of a large congenital fibrosarcoma.

Cytogenetic, immunocytochemical, and ultrastructural studies were performed on a large congenital fibrosarcoma. To our knowledge, this is the first report of a congenital fibrosarcoma characterized by all of these techniques. The findings of immunochemical and electron microscopic studies supported the suggestion that the tumor is of fibroblastic origin. The karyotype of the tumor (48,XY,+11,+20) is similar to that observed in previously reported cases and substantiates the hypothesis that congenital fibrosarcoma is characterized by nonrandom gain of chromosomes.

Calcium↗

[Sclerosing epithelioid fibrosarcoma: a clinicopathologic study of eight cases].

OBJECTIVE: To study the clinicopathologic features, immunophenotype and differential diagnosis of sclerosing epithelioid fibrosarcoma (SEF). METHODS: Eight cases of SEF were investigated by light microscopy and immunohistochemistry. RESULTS: There were five males and three females. Clinically, most patients presented as a slowly growing mass. Six tumors were located in the extremities or limb girdles, and two in the trunk. Grossly, most lesions were relatively well-circumscribed with a nodular or lobulated appearance. They ranged from 2.0 to 10.5 cm in size (mean 6 cm). On sectioning, they had a gray-whitish cut surface and were firm in consistency. Microscopically, the tumors were composed of uniformly round or polygonal epithelioid cells with clear to eosinophilic cytoplasm. The tumor cells were arranged predominantly in single strands or cords and embedded in a heavily hyalinized matrix. In some areas, nests, sheets, acini or alveolar structures were also noted. Nuclei atypia and brisk mitotic activity was not evident. The mitotic count measured less than 1 per 10 high power fields. However in two cases, focal areas exhibited increased cellularity, nuclei atypia and higher mitotic activity, resembling conventional fibrosarcoma. Immunohistochemically, the tumor cells showed diffuse and strong positivity for vimentin and focal or weak positivity for EMA. There was no expression for AE1/AE3, S-100 protein, HMB45, alpha-SMA, MSA, desmin, CD34, bcl-2, CD30 and LCA. Follow-up information in six patients revealed local recurrence in 3 cases and lung metastasis in 1 case. CONCLUSIONS: SEF is a rare variant of fibrosarcoma. Despite the relatively bland appearance and low mitotic activity, the tumor is capable of local recurrence and distant metastasis. Thus, it should be considered and treated as a low to intermediate grade sarcoma. SEF needs to be differentiated from a variety of benign or malignant tumors exhibiting epithelioid features and sclerotic stromal response.

Adult↗

Dynamic evaluation of 18F-FDG uptake by microPET and whole-body autoradiography in a fibrosarcoma-bearing mouse model.

BACKGROUND AND PURPOSE: Fluorine-18-2-deoxy-D-glucose (18F-FDG) has been used in the clinic as a diagnostic radiotracer for monitoring many kinds of tumors, but its value for monitoring fibrosarcoma is not well established. METHODS: In this study, the uptake of 18F-FDG in a fibrosarcoma-bearing mouse model was evaluated using the high resolution positron emission tomography (PET) system microPET. Tumor cells were implanted in 3 FVB/N mice, and static microPET scanning was performed on day 1, 7, 12 and 15 after implantation. A dynamic microPET image was scanned on day 12 to determine the 18F-FDG uptake in 3 other tumor-bearing mice. Time-activity curves were plotted by drawing regions of interest in the tumor, liver, kidneys and muscles. The mice were sacrificed after dynamic microPET imaging and whole-body autoradiography (WBAR) was performed. For biodistribution study, 9 tumor-bearing mice, 3 per experimental group, were studied at 3 time points and the results were compared with the static microPET images. RESULTS: MicroPET images suggested that 18F-FDG could be used to monitor the growth of tumors 7 days after implantation. Dynamic scans of 18F-FDG uptake reached a plateau in the tumor after 20 minutes on day 12 after implantation. Both microPET and WBAR revealed evidence of tumor necrosis. The results of biodistribution and WBAR agreed with those from microPET images. CONCLUSION: MicroPET was useful for monitoring the growth of fibrosarcoma and determination of the maximal uptake time point of 18F-FDG in tumors in this tumor-bearing mouse model.

Animals↗