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Properties of monocyte chemotactic and activating factor (MCAF) purified from a human fibrosarcoma cell line.

A monocyte chemotactic and activating factor (MCAF) has been purified from TNF-stimulated 8387 human fibrosarcoma cell line-conditioned media. The purified MCAF showed microheterogeneity yielding two bands on SDS-PAGE analysis. Fibrosarcoma-derived MCAF specifically competed with THP-1 (a human monocytic cell line)-derived 125I-labeled MCAF in binding to human PBMC, whereas a similar basic heparin-binding leukocyte chemoattractant, IL-8, did not. The purified MCAF stimulated superoxide anion and N-acetyl beta-D glucosaminidase-releasing activity in human monocytes, as well as monocyte cytostatic augmenting activity against tumor cells and chemotactic activity for monocytes. When injected subcutaneously into Lewis rat ears, the purified human MCAF also induced considerable in vivo local monocyte infiltration beginning at 3 h and becoming maximal at 18 h. In conclusion, the data presented in this paper indicate that MCAF is a potent activator of monocytes as well as a monocyte recruitment factor that acts through receptors that are specific for this novel molecule. This novel cytokine might have an important role in tumor growth control due to its ability to attract and activate monocytes.

Acetylglucosaminidase↗

Assessment of growth potential by MIB-1 immunohistochemistry in ameloblastic fibroma and related lesions of the jaws compared with ameloblastic fibrosarcoma.

Specimens from two ameloblastic fibromas (including one recurrent case), two ameloblastic fibro-odontomas, and one ameloblastic fibrosarcoma were subjected to investigation by MIB-1 immunohistochemistry in order to elucidate the growth potential of these tumors. MIB-1 labeling indices in the epithelial component of these tumors ranged from 2.9 to 7.5%, whereas those in the mesenchymal component ranged from 1.5 to 13.5%. Of these, labeling indices in the mesenchymal component of the recurrent ameloblastic fibroma and ameloblastic fibrosarcoma were quite high. These findings suggest that evaluation of growth potential in ameloblastic fibroma and related lesions could be of help in understanding tumor aggressiveness and in selecting appropriate surgical procedures.

Adolescent↗

Inflammatory myofibroblastic tumor (inflammatory fibrosarcoma) of the bone.

Although inflammatory myofibroblastic tumors, originally described in the lung, have recently been recognized to occur in various sites, their origin in bone is exceptional. We present a case of inflammatory myofibroblastic tumor, so-called inflammatory fibrosarcoma, of the bone. The tumor occurred in the iliac bone of a 70-year-old woman. Standard radiographs and magnetic resonance imaging revealed a destructive bone tumor that expanded into the soft tissue. Although the patient underwent excision of the hemi-iliac bone, multiple pulmonary metastases were noted 1 year after the operation. On histologic examination, the tumor was found to be composed of a sarcoma-like cellular area and a hypocellular fibrous area. Inflammatory cell infiltration into the tumor was a distinctive feature and is analogous with that of conventional inflammatory myofibroblastic tumor or inflammatory fibrosarcoma of the soft tissue. This is the first report to our knowledge of an inflammatory myofibroblastic tumor of the bone with distant metastasis.

Aged↗

[Consideration of simultaneous combination chemotherapy--employing a sensitivity test in Dunn osteosarcoma and NR fibrosarcoma by intra-test tube contact of tumor cell suspension, and subcutaneous inoculation].

Fundamental concepts of combination multi-drug chemotherapy have not been well recognized from the aspects of chemo-sensitivity test upon malignant tumors. A chemo-sensitivity test by in-vitro bioassay for Dunn osteosarcoma and NR fibrosarcoma was developed by us to study the simultaneous interactions between two anticancerous agents. 0.1 ml of cell suspension of either mouse sarcoma was immersed in 0.4 ml of RPMI 1640 cell culture medium containing an anticancerous agent such as Mitomycin (MC), Cyclophosphamide (CPM), Vincristine (VC), Bleomycin (BM), 5-FU, Adriamycin (ADM), Cisplatin (CDDP) or Methotrexate (MTX) in a test-tube, and incubated at 37 degrees C for 3 or 6 hours. Then, the sedimented cell suspension of 0.1 ml was inoculated subcutaneously in the dorsum of C3H mouse which provided 4 sites for 4 different sensitivity tests. In 3 weeks, sensitivities of the anticancerous agents were evaluated as positive sensitivity if no growth of the tumor was observed, or negative sensitivity if the growth of more than 10 mm in diameter was observed. Then, the determination of antitumorous effect on 2-drug combination out of the 8 anticancerous agents, were performed on each mouse sarcoma by the same method. In Dunn osteosarcoma or NR fibrosarcoma, the combination of 2 sensitivity-positive agents revealed no apparent synergistic effects. In any combinations of one sensitivity-positive agent with the other sensitivity-negative agent, except the combinations with CPM which possessed mighty antitumorous effect, apparent reduction of antitumorous effects was observed. The combination of 2 sensitivity-negative agents never produced any antitumorous effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Marker polypeptides distinguishing between cancer cell clones with high and low potential for spontaneous metastasis in murine fibrosarcoma cells.

Consistent differences in expression of specific proteins were observed between numerous cancer cell clones with high and low potential for spontaneous metastasis. Seventeen clones from two unrelated murine fibrosarcomas were examined concomitantly for spontaneous formation of lung metastases and for occurrence of individual polypeptide differences by high resolution two-dimensional gel electrophoresis. One of the identified marker polypeptides, designated Hi:2, was very strongly expressed by all 10 strongly metastatic clones, but was absent from 6 and only weakly expressed by one of the 7 weakly metastatic clones. Another marker polypeptide, designated Lo:6, was consistently most strongly expressed by the weakly metastatic clones. Among the approximately 2000 individually separated cellular polypeptides, only these two marker polypeptides consistently distinguished between the strongly and weakly metastatic clones from both fibrosarcomas. Five other polypeptides also distinguished between highly and weakly metastatic clones, but not as stringently.

Animals↗

Juvenile fibrosarcoma of the orbit and eyelid. A study of five cases.

Five patients had juvenile fibrosarcoma of the orbit and eyelid. At initial surgical intervention, the patients ranged in age from newborn to 8 years (mean, 3 years 9 months). Three patients were male and two were female. Proptosis and/or painless swelling of the eyelid were the most common signs and symptoms. Four tumors grew within a few weeks or months, and all five were poorly circumscribed. They were composed of immature, spindle-shaped fibroblastic cells in a classic herringbone pattern or in interlacing fascicles. Hypercellularity and mitotic activity were present in all lesions. The differential diagnosis included rhabdomyosarcoma, fibromatosis, and fibrous histiocytoma. Electron microscopy confirmed the fibroblastic nature of the tumor cells in three cases. Follow-up ranged from one to 32 years (median, seven years). Two of five tumors recurred locally but none metastasized. Apparently surgical excision is the treatment of choice and the tumor has a favorable prognosis.

Child↗

Fibrosarcoma of the head and neck. The UCLA experience.

Between 1955 and 1987, twenty-nine patients with the diagnosis of fibrosarcoma of the head and neck were seen at the UCLA Medical Center. Follow-up ranged from 15 to 192 months, with a median of 66 months. Absolute 5-year survival was 62% (13/21). Five of 17 patients treated initially with surgery alone achieved local control and long-term survival. All five had low-grade lesions. Five patients received postoperative radiation therapy because of positive surgical margins. Three were rendered disease free, and all had low-grade lesions. Radiation therapy was used as primary treatment in six patients, four of whom received additional chemotherapy. Of these six, two are disease free with longer than 5-year follow-up. Surgery with and without adjuvant therapy successfully salvaged 42% (5/12) of the patients with local recurrence. Eighty percent (12/15) of the patients with low-grade lesions were ultimately rendered disease free vs only 8% (1/12) of the patients with high-grade histologic features. Seventy-two percent (13/18) of the patients with local recurrence were known to have positive surgical margins. Sixty-eight percent (13/19) of the patients with recurrent disease had high-grade lesions and/or tumor size larger than 5 cm. Tumor grade is the most important prognostic factor followed by tumor size and surgical margin status. Patients with low-grade lesions and adequate surgical margins are treated well with surgery alone. Patients with high-grade lesions or positive surgical margins should receive adjuvant treatment.

Adolescent↗

MCA106 fibrosarcoma cells transduced with granulocyte/macrophage colony-stimulating factor are not superior to the wild-type cells in suppressing the growth of hepatic metastases.

BACKGROUND AND OBJECTIVES: Vaccination with cytokine gene-modified tumor cells augments the immune response against established tumors and protects against tumor challenges. In this study, we investigated the vaccine potential of GM-CSF-transduced MCA106 fibrosarcoma (MCA-GMCSF) cells in the C57BL/6 (B6) murine hepatic metastasis model. METHODS: Experimental mice received one to three weekly vaccines (subcutaneous/intramuscular, s.c./i.m.) of irradiated, parental, or GM-CSF-transduced MCA106 tumor cells. One week after the last immunization, hepatic metastases were established through the intrasplenic injection of live MCA106 parental (MCA106P) tumor cells. The animals were then sacrificed 3-4 weeks after surgery for evaluation of hepatic tumor burden. RESULTS: Based on in vivo experiments, both GM-CSF-modified and parental MCA106 tumor cell vaccines induced strong protection against hepatic tumor growth with grossly visible tumors rarely identified. This protection was evident even at a single vaccine dose of as low as 1x10(5) irradiated cells. Unimmunized control mice, on the other hand, consistently developed substantial hepatic tumors. Cytotoxicity assays on splenocytes (cultured in vitro for 4-5 days) showed that both groups of vaccinated mice developed strong tumor-specific cytotoxic T-lymphocyte (CTL) responses. Immunohistochemical analysis of injection sites showed infiltration of dendritic cells (DCs) and macrophages into subcutaneously injected MCA-GMCSF cells. Mostly macrophages, however, were seen at the injection site of MCA106P cells. Furthermore, the MCA106P cells expressed high levels of MHC class I antigens and the level of expression was not significantly altered by transduction with the GM-CSF gene. The high expression of MHC class I antigens probably contributed to the strong immunogenicity of the MCA106P cell vaccine. CONCLUSIONS: This study demonstrates that MCA106 parental cells are as effective as the GM-CSF-transduced cells in suppressing the growth of hepatic metastases. The cellular immune responses induced by these two vaccines, however, are probably mediated by different subsets of host effector cells. These results have important implications for the use of GM-CSF-transduced cell vaccines in the immunotherapy of tumors that have the propensity to metastasize through the lymphatic channels and the circulatory system.

Animals↗

Abrogation of lung metastasis of human fibrosarcoma cells by ribozyme-mediated suppression of integrin alpha6 subunit expression.

The interaction of tumor cells with the basement membrane plays a crucial role in tumor metastasis. VLA-6 (alpha6beta1) integrin is one of the major surface receptors for the basement membrane, specifically recognizing laminin. To study the role of VLA-6 integrin in tumor invasion and metastasis, we synthesized a ribozyme that selectively degrades the integrin alpha6 subunit mRNA. The catalytic activity of the ribozyme was verified by in vitro cleavage of alpha6 subunit mRNA. Introduction of the anti-alpha6 ribozyme gene into the human fibrosarcoma cell line HT1080 yielded stable transfectants, which expressed a significantly reduced level of integrin alpha6 mRNA. Flow cytometric analysis showed that the surface expression of VLA-6, but not other integrins, was reduced by approximately 70% in transfected cells. Ribozyme-transfected cells were less adherent to laminin-coated substrata and less invasive into reconstituted basement membrane than mock-transfected cells. When injected i.v. into nude mice, ribozyme-transfected cells produced no lung metastasis in all except 1 of 35 mice, though mock-transfected cells produced multiple lung metastases in 22 of 29 mice. Our results indicate that VLA-6 integrin plays a critical role in tumor invasion and metastasis and may serve as a potential target for eradication of tumor metastasis in the lung.

Animals↗

Suppression of human fibrosarcoma cell growth by transcription factor, Egr-1, involves down-regulation of Bcl-2.

Previously, we showed that the transcription factor Egr-1 suppressed the proliferation of v-sis transformed NIH3T3 cells and also a number of human tumor cells. Here, we investigate the possible mechanisms responsible for this function. We show that transfected Egr-1 in human fibrosarcoma cells HT1080 leads to down-regulation of Bcl-2. Transient CAT transfection assays reveal that expression of Egr-1 suppresses Bcl-2 promoter activity in a dose-dependent manner. Furthermore, overexpression of Bcl-2 in Egr-1-expressing HT1080 cells enhanced cell proliferation in monolayer culture and increased anchorage-independent growth. Our results suggest that suppression of tumor cell proliferation by Egr-1 may be at least partially mediated through the down-regulation of Bcl-2.

Blotting, Western↗

Vascular endothelial growth factor-induced tumor angiogenesis and tumorigenicity in relation to metastasis in a HT1080 human fibrosarcoma cell model.

Although vascular endothelial growth factor (VEGF) is well known to be a potent mitogen for vascular endothelial cells, the role of VEGF in a developmental process of tumor angiogenesis and metastatic potential remains poorly understood. The present study was designed to investigate VEGF-induced vascular formation from a spatiotemporal viewpoint and to analyze VEGF-enhanced metastatic potential using stable clones of HT1080 human fibrosarcoma cells transfected with VEGF cDNA (S) or with vector alone (V). Microangiography revealed massive angiogenesis in the S cell-derived tumors and demonstrated that the angiogenesis occurred not in the tumor itself, but rather around the S cell tumor early after inoculation into the thigh muscles of mice. Thereafter, the angiogenesis extended in and around the tumor. The tumorigenicity of the S cells was higher than the V cells in the subcutaneous (s.c.) space, intraperitoneal space, liver and spleen. However, neither S cells nor V cells metastasized to the liver after an intrasplenic injection. Few apoptotic cells were detected in the S cell tumor, but many apoptotic cells were scattered in the V cell tumor. Our results indicate that VEGF facilitates tumorigenicity in various organs, possibly due to inducing angiogenesis in and around the tumor and preventing tumor cells from undergoing apoptosis, and suggest that VEGF may augment metastatic potential, by accelerating proliferative activity after reaching the target organ. Furthermore, VEGF-induced angiogenesis occurred preferentially around the tumor at an early period of tumor development, followed by neovascularization into the tumor.

Animals↗

Independent regulation of matrix metalloproteinases and plasminogen activators in human fibrosarcoma cells.

Serine proteases and matrix metalloproteinases have been shown to often cooperate in multiple physiological and pathological processes associated with changes in the extracellular matrix (ECM). We have examined the interaction between the plasminogen activator (PA)-plasmin system and matrix metalloproteinases (MMPs) in HT1080 human fibrosarcoma cells treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). While TPA treatment evoked a temporary increased expression of urokinase type PA (uPA), the production of both types of human plasminogen activator inhibitors (PAI) was induced and sustained over 12 h by TPA treatment shifting the protease-protease inhibitors balance in favor of the inhibitors. TPA treatment of HT1080 cells induced the expression of interstitial collagenase (MMP-1) and increased the expression of gelatinase B (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and MT-MMP, a membrane-bound activator of progelatinase A (proMMP-2), while MMP-2 and TIMP-2 expression were decreased. Increased MT-MMP expression by TPA treatment was associated with increased activation of proMMP-2. These data show that the regulation of PA-plasmin and metalloproteinase and their specific inhibitors is uncoordinated. In addition, inhibition of the PA-plasmin system by PAI-2 or aprotinin did not prevent the activation of proMMP-2 by TPA, suggesting that plasmin is not involved in MT-MMP-mediated activation of proMMP-2.

Aprotinin↗

Fibrosarcoma in infants and children: a review of 110 cases.

This retrospective study summarizes the clinicopathologic findings in 110 children with fibrosarcoma. Seventy cases were selected from previous reports and 40 were from our files. The histologic criteria used for diagnosis are the same as those used for adults. Sixty-eight patients were in the first quinquennium of life, 13 in the second, and 29 in the third. Eleven patients died of their tumor, three in the first quinquennium and eight in ght third. Our findings indicate that children who are less than 5 years old have a 7.3% chance of developing metastatic spread even though the local recurrence rate is 43%. Children who are 10 years old or older had a metastatic rate of 50% at 5-year follow-up, a figure closely approximating that for adults. We believe that infants and children less than 5 years old may be treated initially by local excision of the lesion, without sacrificing significant function of the part. Recurrent tumor does not seem to predispose to metastatic disease.

Adolescent↗

Pituitary fibrosarcoma secondary to radiation therapy.

A patient who received postoperative radiation therapy for the treatment of a chromophobe adenoma developed a fibrosarcoma of the pituitary gland region 10 years later. A single course of irradiation was given with a total dose to the pituitary of 4092 rad in 21 fractions and 29 days using Cobalt 60 radiation at a source to skin distance of 80 cm.

Adenoma, Chromophobe↗

The significance of fractionation regimens in radiation and combined hyperthermia using a murine fibrosarcoma.

The significance of time-dose relationships in the use of local tumor hyperthermia (LTH) when combined with radiation (RAD) was studied in a murine fibrosarcoma. RAD, either alone or combined with LTH, was delivered in four equal fractions (total doses, 1.8 to 4.2 krad) separated by 1 to 4 days. LTH (43.1 C +/- .05 C for 15 minutes, water bath) was applied immediately after RAD. In this tumor system, RAD was most effective when delivered every 2nd or 3rd day, by a factor of 1.25 over the response achieved when the four fractions were delivered every 1 or 4 days. At all levels studied, RAD + LTH produced a superior tumor response compared to RAD alone. The ratio of the RAD + LTH/RAD doses to achieve an isobiological response ranged from 1.7 to 2.5. Most significant was the finding that the RAD + LTH treatment response was independent of the fractionation scheme used and more dependent on the total RAD dose delivered.

Animals↗

Ultrastructure of a primary fibrosarcoma of the human thyroid gland.

A primary fibrosarcoma of the thyroid occurring in a patient with a nodular goiter is described. Light microscopy showed interwoven bundles of spindle cells admixed with plump ovoid cells, and foci of multinucleated giant cells. Remnants of distorted thyroid follicles were found only at the periphery of the tumor. "Transitional" epithelial elements were not discernible but the tumor resembled an anaplastic giant cell carcinoma. Multiple blocks studied by electron microscopy, however, revealed that the tumor cells, including the giant cells, have the ultrastructure features of a fibroblast.

Aged↗

Production of plasminogen activator by a primary HSV-2-induced hamster fibrosarcoma and its in vivo derived sublines.

The plasminogen activator (PA) content of a primary HSV-2-induced hamster fibrosarcoma and sublines derived from its in vivo metastases was investigated using the indirect 125I-labeled fibrin plate method. Fresh tissue culture lines established from primary HSV-2-333-2-26 tumors were shown to produce levels of PA similar to sublines derived from lung or kidney foci that developed after resection of primary tumors. In comparison, normal hamster embryo fibroblast (NHEF) and baby hamster kidney cells produced little or no PA, although baby hamster lung fibroblasts produced intermediate levels of PA. In addition, no correlation was found between PA levels of the sublines and their ability to metastasize from subcutaneous tumors, although tumor cell lines were shown to produce significantly more PA than normal cells.

Animals↗

Congenital fibrosarcoma. Preoperative chemotherapy and conservative surgery.

Three cases of congenital fibrosarcoma are reported. The use of preoperative chemotherapy, a VAC regimen, allowed conservative surgery in two of them. The three children are well, with no evidence of disease and without sequelae after completion of postoperative chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗