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PubMed2004

[Inhibition effect of glycyrrhizin on transplanted mandibular gland fibrosarcoma of mice].

OBJECTIVE: To study glycyrrhizin's anticancer effect and its mechanism. METHODS: 3-methylcholanthrene were injected into mice's submandibular glands to induce tumor, then transplanted the tumor pieces (1 mm3) to mice. The transplanted tumors were measured, and flow cytometry analysis and cytomorphology observation were conducted. RESULTS: Glycyrrhizin (GL) inhibited the transplanted mandibular gland fibro-sarcoma of mice and the suitable GL dose for inhibiting fibrosarcoma of mice was 1.61 mg per 20 g weight. The GL dose below 3.22 mg per 20 g weight didn't produce remarkable toxicity and side effects. GL induced cytomorphological changes of tumor cells and enhanced immunosuppression of macrophage on fibrosarcoma. The result of flow cytometry showed that tumor cell counts of GL1 and GL2 groups increased remarkably in DNA synthetic prophase, and decreased in DNA synthetic phase. CONCLUSION: GL can inhibit transplanted mandibular gland fibro-sarcoma of mice. The anticancer mechanism of GL may be acting on related enzymes with phagocytosis. The result of flow cytometry showed that the shift of fibrosarcoma cells from G1 phase to S phase was blocked. This suggests that the anticancer action of GL is related to its inhibition of ribonucleotide reductase, a rate-limiting enzyme in DNA synthesis.

Animals↗
PubMed2004

Sclerosing epitheloid fibrosarcoma. A report of two cases.

Sclerosing epitheloid fibrosarcoma is a rare, histologically well-defined member of adult fibrosarcoma group of soft tissue tumors. Its main histological features are nests and cords of rounded tumor cells surrounded by hyalinized collagenous stroma. Epitheloid appearance with marked sclerosis and infiltrating growth pattern, along with occasional immunohistochemical positivity for epithelial markers may be highly suggestive of infiltrating carcinoma. Despite of bland cytological features clinical course is often protracted with a high local recurrence rate and late metastases. In this report, we present histopathological characteristics of two cases of sclerosing epitheloid fibrosarcoma, together with their clinical presentation, follow-up information and differential diagnosis.

Adult↗
PubMed2005

Down-regulation of overexpressed sp1 protein in human fibrosarcoma cell lines inhibits tumor formation.

Sp1 is a transcription factor for many genes, including genes involved in tumorigenesis. We found that human fibroblast cells malignantly transformed in culture by a carcinogen or by stable transfection of an oncogene express Sp1 at 8-fold to 18-fold higher levels than their parental cells. These cell lines form fibrosarcomas in athymic mice with a very short latency, and the cells from the tumors express the same high levels of Sp1. Similar high levels of Sp1 were found in the patient-derived fibrosarcoma cell lines tested, and in the tumors formed in athymic mice by these cell lines. To investigate the role of overexpression of Sp1 in malignant transformation of human fibroblasts, we transfected an Sp1 U1snRNA/Ribozyme into two human cell lines, malignantly transformed in culture by a carcinogen or overexpression of an oncogene, and into a patient-derived fibrosarcoma cell line. The level of expression of Sp1 in these transfected cell lines was reduced to near normal. The cells regained the spindle-shaped morphology and exhibited increased apoptosis and decreased expression of several genes linked to cancer, i.e., epithelial growth factor receptor, urokinase plasminogen activator, urokinase plasminogen activator receptor, and vascular endothelial growth factor. When injected into athymic mice, these cell lines with near normal levels of Sp1 failed to form tumors or did so only at a greatly reduced frequency and with a much longer latency. These data indicate that overexpression of Sp1 plays a causal role in malignant transformation of human fibroblasts and suggest that for cancers in which it is overexpressed, Sp1 constitutes a target for therapy.

Animals↗
PubMed2005

Congenital fibrosarcoma of the upper extremity--a case report and review of literature.

Fibrosarcoma is rare in pediatric age group. Its diagnosis in infants may be difficult clinically and histologically. A twenty-day infant presented with a rapidly growing mass in the right forearm. Histologically a gray white fleshy mass was seen occupying the entire forearm and distal arm. The tumor showed sheets of closely packed spindle cells with minimal pleomorphism. The cells were positive for vimentin, negative jor smooth muscle actin, desmin and S-100. The diagnosis of congenital fibrosarcoma was made. Most cases of infantile fibrosarcomas present in the first year of life and although they have an alarming presentation, in children they have a much better prognosis as compared to adults. Diagnosis can be made on histology with immunohistochemistry.

Arm↗
PubMed2006

Fibrosarcoma originating in the mandible.

Fibrosarcoma is a malignant mesenchymal neoplasm of fibroblasts that rarely affects the oral cavity and can cause local recurrences or metastasis. In this article we describe a case of primary fibrosarcoma in the mandible in a 16-year-old girl. Microscopically the tumor showed an intense proliferation of spindle-shaped cells, varying little in size and shape and arranged in parallel bands, partly crossing each other, the mitotic activity was increased and there was nuclear pleomorphism. Immunohistochemically the cells only showed immunoreactivity for vimentin and negativity for S-100 protein, CD 68, cytokeratin cocktail, HMB-45, CD34, pan actin HHF 35, desmin, smooth muscle actin and epithelial membrane antigen (EMA). Based on clinical, radiological, histological and immunohistochemical findings the final diagnosis was high-grade intra-osseous fibrosarcoma. The treatment choice was radical surgery with mandibular reconstruction. After one year and nine months of the treatment the patient displayed multiple metastases. Radiation therapy and chemotherapy were used as adjuvant treatment. Unfortunately, the girl died two years after initial diagnosis.

Adolescent↗
PubMed1992

Nonglycolytic acidification of murine radiation-induced fibrosarcoma 1 tumor via 3-O-methyl-D-glucose monitored by 1H, 2H, 13C, and 31P nuclear magnetic resonance spectroscopy.

The effects of 3-O-methyl-D-glucose (3-OMG) on subcutaneously implanted murine radiation-induced fibrosarcoma 1 tumor were examined with 2H, 13C, and 31P nuclear magnetic resonance (NMR) in situ. Using 31P NMR, changes in tumor high-energy phosphate metabolism were monitored for 2.5 h after i.p. administration of 3-OMG (8.1 g/kg body weight); tumor pH decreased by a mean maximum of 0.52 +/- 0.05 (SE) (n = 10), [PCr] decreased by 54%, [NTP] decreased by 35%, and [Pi] increased by 36%. Tumor blood flow, as measured by 2H NMR monitoring of D2O washout kinetics, decreased by 40% at 1 h and by 47% at 2 h after 3-OMG injection (n = 4). This substantial tumor acidification (pH decrease much greater than 0.1), expected to require a glycolytic substrate (Hwang et al., Cancer Res., 51: 3108-3118, 1991), is surprising in light of the previously documented metabolically inert nature of 3-OMG. In situ 13C NMR spectroscopy, following [6-13C]3-OMG i.p. injection, examined the possibility of the glycolytic metabolism of 3-OMG. However, only the C-6 resonance of 3-OMG was detected (n = 6); no resonances from [6-13C]3-OMG-6-phosphate or [3-13C]lactate were observed. These results confirmed that 3-OMG was not metabolized in radiation-induced fibrosarcoma 1 tumor. At the completion of the in situ 13C NMR experiments, tumors were freeze clamped, and perchloric acid extraction was performed. High-resolution 1H NMR measurement of lactate concentrations showed no statistically significant difference in control tumor extracts (from mice not receiving i.p. injection; n = 5) and in tumor extracts from mice administered i.p. [6-13C]3-OMG (n = 5), indicating that there was no significant increase in lactate level in the tumor extracts from mice administered i.p. 3-OMG due to increased plasma glucose concentration. The results of these 1H and 13C NMR studies indicated that the radiation-induced fibrosarcoma 1 tumor acidification caused by i.p. administration of 3-OMG was not due to a direct (3-OMG----lactate) or an indirect (systemic glucose----lactate) increase in tumor lactic acid levels.

3-O-Methylglucose↗
PubMed1991

Antitumor effect of echitamine chloride on methylcholonthrene induced fibrosarcoma in rats.

Echitamine chloride a plant alkaloid from Alstonia scholaris has been used to examine the anticancer effects on methylcholanthrene-induced fibrosarcoma. Echitamine chloride dissolved in saline (10 mg/kg body weight) and injected subcutaneously for 20 days in fibrosarcoma rats has exhibited significant regression in tumor growth. The altered activities of plasma and liver transaminases and gamma-glutamyl transpeptidase and lipid peroxidation in fibrosarcoma have been corrected to near normal after echitamine chloride treatment. The decreased liver glutathione content and the lowered activities of glutathione peroxidase, superoxide dismutase and catalase have also been reversed to near normals after echitamine chloride treatment.

Alkaloids↗
PubMed1991

[A case of primary fibrosarcoma caused by spontaneous intracerebral hematoma].

A rare case of repeated intracerebral hematoma associated with an intracerebral fibrosarcoma is reported. A 43-year-old man was referred to our clinic with headache and vomiting of sudden onset. On admission, he was lethargic. CT revealed a huge intracerebral hematoma in the left temporal lobe with midline shift. Angiography failed to demonstrate any evidence of an intracranial tumor. An operation was performed under the diagnosis of an idiopathic cerebral hematoma. The postoperative course was uneventful and he was discharged without any deficits except for a left upper quadrant homonymous hemianopia. Four and a half months after the first operation, he was readmitted to our clinic with the same symptoms as he had at the first admission. Neuroradiological examination again revealed an intracerebral hematoma in the left temporal lobe. At operation, a pinkish-gray discolored mass at the hematoma wall was found. An intraoperative histological examination of the mass indicated a malignant tumor and the tumor was totally removed. However the patient did not recover from the severe neurological deficits and died 3 months after the second surgery. Histological examinations of the tumor demonstrated a typical fibrosarcoma. Intracerebral primary fibrosarcoma with hemorrhage is quite rare. In such a case with a large hematoma, the presence of a tumor may be obscured on CT scan and angiography. Detailed observation of the hematoma wall using an operating microscope should be performed to allow a correct diagnosis.

Adult↗
PubMed1991

Role of laminin-binding integrin in the invasion of basement membrane matrices by fibrosarcoma cells.

Laminin is a large glycoprotein that is found in basement membranes and promotes cell adhesion and migration. In human fibrosarcoma cells we detected the presence of an integrin complex, with a Mr of 140,000/120,000 under nonreducing conditions, that bound specifically to laminin-Sepharose columns. Immunoprecipitation with monoclonal antibodies characterized this complex as alpha 6 beta 1. Attachment of the fibrosarcoma cells to laminin substrates was completely inhibited in the presence of anti-alpha 6 beta 1 antibody, while attachment to fibronectin and type IV collagen was unaffected. When seeded onto reconstituted basement membrane, the fibrosarcoma cells spread out, migrated, and invaded the matrix. In the presence of anti-beta 1 or anti-alpha 6 beta 1 antibodies, initial invasion through the matrix was inhibited. The results indicate that the HT1080 cells express the alpha 6 beta 1 complex and that it mediates their attachment to laminin. Furthermore, this receptor appears to be important during initial attachment and subsequent invasion of basement membrane-like matrices.

Amino Acid Sequence↗
PubMed1990

Definition of a sequence, RYVVLPR, within laminin peptide F-9 that mediates metastatic fibrosarcoma cell adhesion and spreading.

A synthetic peptide from the inner globule of the B1 chain of laminin, termed peptide F-9 (RYVVLPRPVCFEKGMNYTVR; residues 641-660), has been shown to have heparin-binding and cell adhesion-promoting activities for diverse cell types (Charonis et al., J. Cell. Biol., 107: 1253-1260, 1988). In this study, the metastatic murine fibrosarcoma cell line, UV-2237-MM, adhered and spread on surfaces coated with laminin and peptide F-9 in a concentration- and time-dependent fashion. Cells migrated toward laminin in Boyden microchemotaxis chambers but not toward peptide F-9. However, exogenous soluble peptide F-9 inhibited both the adhesion and migration of cells toward laminin. Polyclonal antibodies raised against peptide F-9 were capable of inhibiting laminin-mediated cell adhesion and migration. Peptide F-9 is located 265 residues from CDPGYIGSR, another sequence on the B1 chain of laminin which has been reported by others to promote cell adhesion (Graft et al., Cell, 48: 989-996, 1987). In contrast to peptide F-9, various control peptides including CDPGYIGSR did not promote the adhesion, spreading, or migration of the UV-2237-MM fibrosarcoma cells. In addition, neither exogenous peptide CDPGYIGSR nor antibodies raised against peptide CDPGYIGSR were capable of inhibiting laminin-mediated cell adhesion or migration. These results indicate that peptide F-9, but not peptide CDPGYIGSR, represents a major fibrosarcoma cell adhesion-promoting domain on intact laminin. A series of overlapping peptides were synthesized which contained various portions of the parent peptide F-9. The use of these peptides in cell adhesion assays demonstrated that the sequence RYVVLPR from the amino terminus of peptide F-9 was essential for cell adhesion-promoting activity.

Amino Acid Sequence↗
PubMed1990

Site-dependent differences in response of the UV-2237 murine fibrosarcoma to systemic therapy with adriamycin.

Murine fibrosarcoma UV-2237MM cells were implanted into different organs of syngeneic C3H/HeN mice. The resultant tumors were treated by i.v. administration of Adriamycin (ADR). Despite the high sensitivity of the fibrosarcoma cells to ADR in vitro, the established tumors growing in vivo exhibited marked differences in their responses to ADR. Tumors growing in the subcutis and the spleen were ADR-sensitive, whereas lung metastases were not. The resistance of lung metastases to ADR was not due to selection of a drug-resistant population since tumor cells isolated from lung metastases were highly sensitive to ADR under in vitro conditions. The responsiveness of skin and spleen tumors to ADR was due neither to increased blood supply nor to preferential accumulation of ADR, since both parameters were higher in lung metastases. Protein kinase C activity levels correlated with ADR resistance in the closely related murine fibrosarcoma cell line UV-2237 and its ADR-selected multidrug-resistant variants. However, nearly identical levels of protein kinase C activity were found in UV-2237MM tumors growing in the lung, spleen, and subcutis, indicating that protein kinase C activity levels did not account for the different responses to ADR. The present studies suggest that the organ environment influences the response of UV-2237MM to ADR administered systemically. This finding may have implications for the design of animal models for therapy of disseminated cancer.

Animals↗
PubMed1990

[A well differentiated fibrosarcoma arising in left neck region].

The frequency of a fibrosarcoma, based on current criteria, is less than 10% of soft tissue sarcomas. It is most common in the region of extremities and the trunk and relatively rare in the head and neck region. Therefore, of interest is a case of a well differentiated fibrosarcoma arising in left neck region of a 69-year-old woman that is reported. The excised tumor consisted of a firm, partially lobulated mass with a fibrous capsule that measured 8 cm at its greatest diameter. Histologically, the tumor tissue was rather uniform and often had a fasciculated growth pattern consisting of spindle shaped cells and interwoven collagenous fiber in a parallel fashion. To achieve a diagnosis, it was necessary to differentiate this type of fibrosarcoma from aggressive fibromatosis and myogenic tumor (leiomyoma or leiomyosarcoma).

Aged↗
PubMed1989

Separation and evaluation of changing pattern of glycosaminoglycans in 3-methyl cholanthrene induced fibrosarcoma.

The present study evaluates the glycosaminoglycans (GAGs) pattern associated with transplantable rat fibrosarcoma induced by 3-methylcholanthrene. The quantitative analysis of fractionation of GAGs in fibrosarcoma and fetal tissues was performed by enzymatic digestion. The average value of total GAGs in fibrosarcoma and fetal tissue was found to be 4 times higher than its value in the tissue of origin. GAG content showed a steady increase from 7th day onward to 25th day. Hyaluronic acid content in tumor tissue was observed to increase markedly (8-fold) against that of the normal tissue and was equivalent to that of the fetal tissue. Chondroitin sulfate level was also increased in the tumor as well as fetal tissue. The increase in the chondroitin sulfate and hyaluronic acid contents might possibly be due to the abnormal GAG metabolism in the increased production of both sulfated and nonsulfated GAGs.

Animals↗
PubMed1989

[Intracranial fibrosarcoma fifteen years after radiotherapy in bilateral retinoblastomas: effect of combined chemotherapy with cisplatin and VP-16].

We report intracranial fibrosarcoma which developed after radiotherapy for bilateral retinoblastomas. A 16-year-old boy was admitted with swelling of his left eyelid as his chief complaint on September 10, 1987. He had a past history of bilateral retinoblastomas at one year of age, which was treated by bilateral ophthalmectomy and postoperative radiotherapy; 50 Gy to right eye and 60 Gy to left eye. Until fifteen years old, he had no trouble except blindness. On admission, a dumb-bell type huge tumor with the destruction of the orbital roof was demonstrated on CT scan and MRI. The tumor was composed of solid orbital tumor and cystic tumor located in the left frontal lobe. On September 18, partial removal of the orbital tumor and evacuation of the intracranial cyst following embolization of the left external carotid artery was performed. The histological diagnosis of the tumor was fibrosarcoma. For the residual tumor, combined radiochemotherapy was carried out. The patient was treated with intravenous administration of 20 mg/m2 of cisplatin and 60 mg/m2 of VP-16 daily for five days and then whole brain radiotherapy of 26 Gy. On March 27, 1988, he obtained a complete remission of the tumor and was discharged without neurological deficit except blindness. In this case, we have presented a radiation-induced secondary tumor after a treatment of bilateral retinoblastomas. Although the tumor was highly proliferative and invasive fibrosarcoma, we could control it well by multimodality treatment including surgery, radiation and chemotherapy. It is noteworthy that combined chemotherapy with cisplatin and VP-16 was effective against this type of tumor.

Adolescent↗
PubMed1988

Induction of lymphomas and fibrosarcomas in nude mice after implantation of simian virus 40-transformed human meningioma.

Human cells transformed by Simian virus 40 (SV40) usually show little or no tumor formation after implantation in nude mice. In long-term studies, however, we have observed that 127 to 366 days after subcutaneous injection of SV40-transformed human meningioma cells (KJ-M2-T) into nude mice (Nu/Cox), 6 of 15 animals developed lymphomas or fibrosarcomas, usually at the site of inoculation. The induced tumors were of murine origin and were positive for SV40-T antigen. Chromosome analysis and G11 staining revealed no evidence of hybridization between human and mouse cells. No spontaneous shedding of SV40 was noted with KJ-M2-T cells in vitro; however, SV40 could be rescued after fusion of KJ-M2-T with BS-C-1 monkey kidney cells, but not with L929 mouse fibroblasts. A parallel study using SV40-transformed human fetal brain cells failed to induce tumors in nude mice despite the demonstration that infectious SV40 could also be rescued from this line after fusion with BS-C-1 but not with L-929. Subcutaneous injection of 5 X 10(3) TCID's of SV40 (strain J436) into nude mice resulted in the induction of fibrosarcomas at the injection site in 6 of 15 mice after 273 to 396 days. The induction of malignant lymphomas after implantation of SV40 transformed cells contrasted with the development of fibrosarcomas after injection of free virus. This study suggests that after subcutaneous implantation into nude mice, some SV40-transformed human tumor cell lines can serve as vectors for transmitting SV40 to murine cells causing transformation and tumor development in the host animal.

Animals↗
PubMed1985

Cross-reactive cellular and humoral immunity to carcinogen-induced chicken fibrosarcomas. I. Protective cross-immunity between transplantable tumor lines.

Dimethylbenz[a]anthracene (DMBA)-induced transplantable fibrosarcomas in B2 homozygous chickens (SC line) grow progressively in normal chickens, but are rejected by chickens immunized previously with irradiated tumor cells and Corynebacterium parvum. Tumor-immune chickens resist challenge by the immunizing tumor lines as well as by some, but not all, fibrosarcoma lines. The pattern of cross-reactivity between four DMBA-induced transplantable tumor lines was examined in detail. Ability to reject a tumor challenge correlated very well (p less than 0.001) with the presence of delayed-type hypersensitivity (DTH) to that tumor. Immunization with one of two of the DMBA-induced lines tested also caused rejection of transplantable tumors developed from methylcholanthrene-induced and benzo(a)pyrene-induced primary fibrosarcomas. Although immunization with tumor caused DTH to chicken embryo fibroblasts (CEF), immunization with CEF failed to cause protective immunity or DTH to tumors. Presence of protective immunity, where tested, also correlated with the ability of spleen cells from immune donors to inhibit tumor growth in Winn tests. Humoral immunity exhibited even greater cross-reactivity than did cellular immunity. Distinct patterns of cross-reactivity were nevertheless observed with respect to the serum antibodies as detected in ELISA. Two of these patterns were also observed in several sera from primary tumor-bearing chickens, both including reactivity with CEF. Such reactivity was absent from normal chicken sera.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Influence of immune status on the metastasis of three murine fibrosarcomas of different immunogenicities.

Three fibrosarcomas of different immunogenicities were tested for their ability to form spontaneous and experimentally induced metastases in normal, sham-suppressed, immunosuppressed, and immunologically restored syngeneic mice. Immunosuppression, achieved by adult thymectomy and sublethal X-irradiation (450 R), affected experimental metastasis of the three tumors in different ways. Upon i.v. injection, the highly immunogenic fibrosarcoma formed more pulmonary tumor colonies in immunosuppressed mice than in normal, sham-suppressed (sham thymectomy and 450 R), or immunologically reconstituted animals (thymectomy, X-irradiation, plus 10(7) normal syngeneic lymphocytes given i.v.). A fibrosarcoma of intermediate immunogenicity also formed more pulmonary metastases in immunosuppressed recipients, but this increase could not be reversed by reconstitution with 10(7) lymphocytes. In contrast, the least immunogenic tumor formed fewer pulmonary tumor colonies in immunosuppressed mice than in normal, sham-suppressed, or immunologically reconstituted mice. We conclude that the role of the immune system in experimental cancer metastasis varies for different tumors and that tumor immunogenicity is an important factor in the relationship between host immunity and tumor dissemination.

Animals↗
PubMed1979

Prognosis after surgical excision of fibrosarcomas in cats.

Forty-four cats from which fibrosarcomas had been excised were studied for a minimum of 3 years, of until death. Two factors, tumor site and mitotic index, were found to be of prognostic significance, but tumor size, duration of growth, and histologic appearance were not. Following removal of fibrosarcomas from the pinna or flank in 6 cats, none died as a result of the tumor but 24 of 35 (70%) cats with fibrosarcoma in the skin of the head, back, or limbs were euthanatized because of local recurrence, usually within 9 months of surgery. The median survival time of cats with a tumor of mitotic index 6 or more in the head, back, or limbs was 16 weeks, compared with 128 weeks when the mitotic index was less than 6. Eleven percent of cats developed pulmonary metastases.

Animals↗