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PubMed1989

Comparison of the effects of retinoids and glucocorticosteroid on protein and type IV collagen synthesis in HT-1080 (human basement membrane forming fibrosarcoma) cells.

The effects of various retinoids and dexamethasone on protein and type IV collagen synthesis were studied in human basement membrane-forming fibrosarcoma (HT-1080) cells. Retinol, etretinate (Ro-10-9359), free acid of etretinate (Ro-10-1670) and 13-cis-retinoic acid (RA) in 10(-7) M concentrations slightly reduced total protein and type IV collagen synthesis in the HT-1080 cells, the largest decrease being found with Ro-10-1670 and 13-cis-RA. In contrast, dexamethasone markedly stimulated the incorporation of [14C]proline and the synthesis of [14C]hydroxyproline, an index of the synthesis of type IV collagen. Part of the increase noted in total protein synthesis and type IV collagen synthesis after dexamethasone was due to enhanced intracellular activity of proline. Retinoids did not markedly affect the specific activity of proline. The addition of 13-cis-RA with dexamethasone also increased total protein and type IV collagen synthesis, but to a lesser extent than did dexamethasone alone. 13-cis-RA did not affect the synthesis of fibronectin, a component of connective tissue matrix, while dexamethasone clearly increased the absolute and relative synthesis of fibronectin. Thus the results indicate that retinoids modulate the metabolism of HT-1080 cells, in a way which is separate from that of glucocorticoids. It is also possible that retinoids used in vivo in clinical practice may modulate the metabolism of the connective tissue matrix of basement membranes, i.e. type IV collagen.

Acitretin↗

PubMed1986

Poorly differentiated fibrosarcoma (spindle cell sarcoma) involving the temporal bone.

A case of metastatic fibrosarcoma of the temporal bone was studied histopathologically. The primary site of this tumor was the posterior neck region. The initial major symptom of the patient was a left facial nerve paralysis. Although the patient underwent a suboccipital posterior craniectomy, radio-, and chemotherapy, she eventually died from multiple metastases. Histological examination of the temporal bones showed an extensive tumor invasion in the external auditory canal, middle ear cavity, middle ear muscle, tympanic membrane, mastoid cavity, petrous apex, facial nerve, and superior division (distal segment) of the vestibular nerve (left ear). The route from the stylomastoid foramen to the superior division of the vestibular nerve via the facial nerve canal could be one of the possible passages of tumor invasion.

Adult↗

PubMed1980

Retroperitoneal fibrosarcoma.

A case of retroperitoneal fibrosarcoma is reported. Clinical and pathological signs of the lesion and its treatment are emphasized.

Adult↗

PubMed1998

Expression of angiostatin cDNA in a murine fibrosarcoma suppresses primary tumor growth and produces long-term dormancy of metastases.

Tumor growth and metastasis are angiogenesis dependent. Previously, we reported that angiostatin, a potent angiogenesis inhibitor, produced by a primary Lewis lung carcinoma suppressed its growth of lung metastases (O'Reilly, M.S., L. Holmgren, Y. Shing, C. Chen, R.A. Rosenthal, M. Moses, W.S. Lane, Y. Cao, E.H. Sage, and J. Folkman. 1994. Cell. 79:315-328). Now we show that a shift of balance of tumor angiogenesis by gene transfer of a cDNA coding for mouse angiostatin into murine T241 fibrosarcoma cells suppresses primary and metastatic tumor growth in vivo. Implantation of stable clones expressing mouse angiostatin in C57Bl6/J mice inhibits primary tumor growth by an average of 77%. After removal of primary tumors, the pulmonary micrometastases in approximately 70% of mice remain in a microscopic dormant and avascular state for the duration of the experiments, e.g., 2-5 mo. The tumor cells in the dormant micrometastases exhibit a high rate of apoptosis balanced by a high proliferation rate. Our study, to our knowledge, for the first time shows the diminished growth of lung metastases after removal of the primary tumor, suggesting that metastases are self-inhibitory by halting angiogenesis. Our data may also provide a novel approach for cancer therapy by antiangiogenic gene therapy with a specific angiogenesis inhibitor.

Angiostatins↗

PubMedDate not supplied

Influence of total parenteral nutrition on tumor growth and polyamine biosynthesis of fibrosarcoma-bearing rats after induced cachexia.

The effect of a protein-free diet (PF) or a restricted intake of chow (RI) and subsequent host repletion with total parenteral nutrition (PF-TPN, RI-TPN) on tumor growth and polyamine metabolism of fibrosarcoma-bearing rats was examined. Host weight was significantly reduced by PF and RI. Tumor growth was reduced in malnourished rats with the PF regimen resulting in the greatest decrease. Rats receiving TPN after 14 days of the RI or PF regimens had higher host weight and plasma albumin levels than malnourished rats. Tumor growth during TPN was evaluated as the percent increase and compared with that of the respective malnourished rats. The percent increase for RI-TPN rats was significantly greater although a trend toward an increase was also evident for PF-TPN rats. Tumor ornithine decarboxylase (ODC) activity and putrescine levels were increased for PF rats and decreased for RI rats while tumor ODC activity was consistently increased by TPN. Tumor growth, ODC activity, and putrescine levels were simultaneously increased only for those rats fed the RI regimen prior to TPN. These results show a disparity in tumor ODC activity, putrescine levels, and tumor growth in malnourished rats. The results of this study suggest that the nutritional origin of cachexia influences the response of the tumor to TPN and emphasizes the importance of considering the methods to induce malnutrition in designing therapuetic regimens.

Animals↗

PubMedDate not supplied

Lysozyme-containing renal tubular hyaline droplets in F344 rats bearing a rat fibrosarcoma-derived transplantable tumor.

Renal tubular hyaline droplets developed in male and female F344 rats bearing a rat fibrosarcoma-derived transplantable tumor (SS). The droplets accumulated exclusively in the proximal renal tubular epithelia as eosinophilic granules of various sizes in hematoxylin and eosin-stained sections. The granules stained bright red with azan-Mallory stain. Immunohistochemically, the droplets were positive for lysozyme to various degrees but were negative for alpha 2u-globulin, albumin, and alpha 1-antitrypsin. These findings indicated the involvement of lysozyme, a low-molecular-weight protein, in the droplet formation. The morphological and immunohistochemical findings of the hyaline droplets bore a close resemblance to those reported in rats as a secondary lesion to spontaneous histiocytic sarcomas. Others have speculated that renal tubular hyaline droplets in histiocytic sarcoma-bearing rats are formed in lysosomes through cellular overload of lysozyme secreted excessively by the tumor cells. However, neoplastic cells of SS tumors were negative to lysozyme. The pathogenesis of renal hyaline droplets appearing in SS tumor-bearing rats remains to be investigated.

Animals↗

PubMed2003

Repair of ascending aortic aneurysm in a patient with fibrosarcoma over sternum.

The combination of an ascending aortic aneurysm and suprasternal soft tissue tumor is rarely reported in the literature. This case involves a 62-year-old man diagnosed with an ascending aortic aneurysm and a fibrosarcoma over the sternum that was successfully treated by surgery. The patient underwent an aortic replacement operation with a Dacron graft and a muscle flap transposition procedure to cover the defect over the sternum.

Aortic Aneurysm↗

PubMedDate not supplied

[Congenital fibrosarcoma (author's transl)].

A case of congenital fibrosarcoma is described and analyzed together with 27 other cases reported in the literature. The rather favourable biologic behaviour justifies conservative therapy based on complete and early surgical resection.

Bone Neoplasms↗

PubMedDate not supplied

Incidence, growth and antigenicity of fibrosarcomas induced by Teflon disc in mice.

Subcutaneous sarcomas were induced in BALB/c, C3Hf/Dp, and C57BL/He female mice by implantation of a Teflon disc or by injection of 7,12-dimethylbenz (a) anthracene (DMBA). The incidence of DMBA tumors was homogeneously high (60-86%) in the 3 strains, and the latency varied from 16 to 26 weeks from treatment. Teflon-induced tumors developed, in the BALB/c, C3Hf/Dp, C57BL/He mice, in 44, 94, and 30%, with a mean latency of 78, 61, and 82 weeks respectively. Evaluation of the growing capacity of 4 DMBA-induced and 14 Teflon-induced fibrosarcomas at the first and second transplant passage showed that Teflon tumors grew faster and needed a smaller cell dose to take than the DMBA tumors. Transplantation type antigens were detected only on the chemically induced tumors. Cross-reacting antigens were detected on 3 of the 5 Teflon-induced tumors by an in vitro assay for cell-mediated cytotoxicity.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Analysis of rabbit and guinea pig complement efficiency in cytotoxicity tests against fibrosarcoma and lymphosarcoma cells.

In a complement-dependent 51Cr cytotoxicity assay, using as target murine fibrosarcoma or lymphosarcoma cells, the rabbit complement (RC) was more efficient than guinea pig complement (GPC) when tested either with strong antisera, such as antihistocompatibility sera, or with weak sera, such as wera from normal mice shown previously to posses a natural antitumor response. The high efficiency of RC was not due to activation by antibodies of a different class or specificity than those activating GPC. In fact, both 2-mercaptoethanol (2-Me)-sensitive or-resistant immunoglobulins could activate both RC and GPC, and the results of absorption tests indicated that the antibodies detected using either of the 2 complements were directed against the same specificities. In addition, the results of tests searching for cooperative antibodies excluded that a cooperative effect might be responsible for the high efficiency of RC. With weak antisera, sera of different rabbits were found to have different complement activity.

Animals↗

PubMedDate not supplied

Immunogenic neoplastic clones derived in vitro from an originally non-immunogenic BALB/c fibrosarcoma.

A non-immunogenic fibrosarcoma (SDC2), obtained by spontaneous neoplastic transformation of BALB/c fibroblasts cultured within a diffusion chamber kept in the peritoneal cavity of (BALB/c x C3Hf)F1 mice, was maintained in tissue culture for 10 passages. Three different clones were then derived from the in vitro neoplastic population. Each of the clones, the original in vivo tumor, and its in vitro line taken at the 10th passage (before cloning) were tested for the presence of individual tumor-associated tramsplantation antigens (TATA) by in vivo growth and excision assay. Contrary to the original SDC2 neoplasm, its in vitro line and 2 out of 3 clones (CL1-SDC2 and CL3-SDC2) were immunogenic, whereas the other clone (CL6-SDC2) displayed no immunogenicity. In addition, CL1-SDC2 and CL3-SDC2 were able to induce a reciprocal cross-protection in in vivo transplantation tests, thus showing common TATA; no cross-reactions were found between these clones and 2 other chemically-induced immunogenic sarcomas. The results suggest an antigenic heterogeneity in the original population of the nonimmunogenic SDC2 sarcoma, with the presence of antigenic but sub-immunogenic neoplastic cells.

Animals↗

PubMed1983

Cytotoxicity of subpopulations of splenic cells from normal and fibrosarcoma - bearing mice towards syngeneic tumour cells.

The nonadherent splenic cells from normal and tumour-bearing (mouse fibrosarcoma-MFS) Swiss mice were divided into 6 subpopulations on Percoll step density gradient and characterised. For the determination of their cytotoxicity towards syngeneic MFS cells and their electrophoretic mobility (EPM), the splenic cell populations were pooled to form 2 broad groups: a lower-density group (density of saline to just less than 1.069 g/ml) and a higher-density group (1.069 to just less than 1.087 gm/ml). In general, the splenic cells from mice bearing 10- to 11-day-old MFS tumours differed in certain characteristics from those of normal mice in that they showed an increase in the following: proliferation, heterogeneity, with appearance of large cells (greater than 70 mu2); cells with a lower density (less than 1.069 g/ml); cells with a lower (less than 0.85 micron/sec/Volt/cm) anodi cEPM. The cytotoxicity studies revealed that: a) the lower-density splenic cells of both normal and tumour-bearing mice were more cytotoxic than the higher-density splenic cells; b) the lower- and higher-density splenic cells of tumour-bearing mice were more cytotoxic than the corresponding cells of normal mice. These findings indicate that the splenic cells of mice with a lower EPM and a lower density are the main contributors of cell-mediated cytolysis of a subpopulation of MFS cells.

Animals↗

PubMed1985

Genetic unresponsiveness to a murine fibrosarcoma determined by the host genetic environment but not by lymphocyte precursor genotype.

(BALB/c X C3Hf) (H-2d X H-2k)F1 hybrid mice but not parental BALB/c or other BALB/c X H-2k F1 hybrids, were unresponsive in transplantation and in neutralization (Winn) assay against a 3-methylcholanthrene-induced BALB/c fibrosarcoma. In BALB/c mice the antitumor activity revealed by Winn assay with antitumor immune lymphoid cells was shown to be tumor specific and mediated by Thy 1+ cells. Mouse chimeras were constructed by injecting fetal liver cells into irradiated recipients. BALB/c----(BALB/c X C3Hf)F1 and control (BALB/c X C3Hf)F1----(BALB/c X C3Hf)F1 chimeras were unable to develop a transplantation immunity against the immunizing tumor, whereas (BALB/c X C3Hf)F1----BALB/c chimeras were able to respond to the immunizing tumor. Thus, unresponsiveness was shown to be due to a defect in the maturation of precursor stem cells both of parental and F1 hybrid origin in the body of the (BALB/c X C3Hf)F1 animals.

Animals↗

PubMed1986

Motility of splenic cells from normal and fibrosarcoma-bearing mice in agarose assay.

When nonadherent splenic cells from normal and tumor-bearing (mouse fibrosarcoma, MFS) Swiss mice were added to wells made in agarose layers in plastic petri dishes, subpopulations of cells from tumor-bearing mice were seen to migrate out of the wells, whereas those from normal mice did not. The proportion of migratory cells among the lower density (less than 1.057 to less than 1.069 g/ml) cells was larger than that of higher density (1.069 to less than 1.087 g/ml) cells. When the plastic surface underneath the agarose layer was covered with a monolayer of MFS cells, the splenic cells from normal mice also migrated out of the wells. About 20% dead MFS cells were observed in the zone of migration when the migratory cells were from normal mice, and about 30% when the migratory cells were from tumor bearing mice. Apart from revealing the differences between the migratory behavior of splenic cells, the present work also suggests a novel application of agarose methodology in the study of interaction of cytotoxic cells with malignant cells.

Animals↗

PubMed2003

Use of a Japanese quail fibrosarcoma cell line (QT-35) in serologic assays to determine the antigenic relationship of avian metapneumoviruses.

The ability of a Japanese quail fibrosarcoma cell line (QT-35) to support the replication of avian metapneumoviruses belonging to the 3 subgroups A (14/1 virus), B (Colorado virus), and C (Hungary virus) enabled the development of assays for the detection and evaluation of virus-specific antibodies. On the basis of the results of enzyme-linked immunosorbent assay (ELISA), plaque reduction neutralization assay (PRNA), immunofluorescent assay (IFA), and Western blot analysis, some degree of antigenic cross-reactivity was observed between prototype viruses belonging to each of the 3 subgroups A, B, and C. The antigen produced in QT-35 cells was found to be superior with respect to its reactivity with virus-specific antibodies, as determined when used in ELISA and IFA. Standardization of both the input virus and the virus-specific antibodies in PRNA enabled a more detailed analysis of the antigenic relationship between these viruses. Specifically, it was observed that 14/1 virus shared more neutralizing regions with Hungary and Colorado viruses than did either of these viruses with 14/1 virus. In addition, Hungary virus shared comparatively fewer neutralizing epitopes with the Colorado virus than did 14/1 virus. Western blot analysis of the reactivity patterns of virus antigen, produced in QT-35 cells, with subgroup-specific antibodies identified a cross-reactive protein migrating at approximately 18 kD. These assays and the information from the Western blot will enable further analysis of avian metapneumovirus isolates to determine antigenic relationships.

Animals↗

PubMed2002

Low-grade fibrosarcoma (hyalinizing spindle cell tumor with giant rosettes) with pulmonary metastases at presentation: case report and review of the literature.

Hyalinizing spindle cell tumor with giant rosettes (HSCT) is presently considered a low-grade fibrosarcoma and is also considered a variant of low-grade fibromyxoid sarcoma by some. None of the HSCTs in the original series had manifested malignant behavior in the form of metastasis, but since that initial report, 2 patients have been reported with pulmonary metastases and another patient with multiple pulmonary nodules in the absence of an identifiable primary tumor. Our patient is the second recorded case of HSCT with pulmonary metastases at the time of diagnosis. A needle biopsy of the axillary mass in the present case consisted mainly of densely hyalinized collagen, whereas the lung nodules had the characteristic giant collagen rosettes surrounded by a bland spindle cell stroma. This case, in addition to at least 2 others in the literature, has demonstrated that the HSCT is a malignant neoplasm with the capacity to metastasize; however, the presence and even persistence of metastatic lesions in the lung has not altered to date an otherwise indolent clinical course. The fact should not be overlooked that the HSCT is a recently reported entity whose natural history and nosology are subjects of continuing observation, study, and discussion.

Adult↗

PubMed1996

Hypercalcemia associated with infantile fibrosarcoma producing parathyroid hormone-related protein.

We describe a 7-month-old boy who manifested severe hypercalcemia associated with mesenchymal neoplasm. A huge hypervascular tumor on the neck had been detected in prenatal ultrasonography. Surgical removal of the entire tumor at birth was not indicated, because the tumor was diagnosed as hemangioma. Chemotherapy and radiotherapy were attempted, but there was no effect on tumor growth. When the infant was 6 months old, the serum calcium level increased rapidly, associated with the expansion of the tumor. Hypophosphatemia due to phosphaturia was also observed. Serum PTH was undetectable, whereas the serum concentration of carboxyl-terminal (C-terminal) fragments of PTH-related protein (PTH-rP) was markedly elevated. Northern blot analysis and immunostaining demonstrated the expression of PTH-rP in the tumor. The tumor was transplantable to nude mice and caused elevation of circulating PTH-rP in the animals. Histological examination of the patient's bone revealed an increased number of osteoclasts. These findings were consistent with humoral hypercalcemia of malignancy caused by the excess production of PTH-rP. The tumor was identified histologically as infantile fibrosarcoma, which has not been reported as a cause of humoral hypercalcemia of malignancy to date. The expression of PTH/PTH-rP receptor messenger ribonucleic acid was detected in the tumor by the RT-PCR, suggesting that PTH-rP may have exerted its effect in the tumor in an autocrine/paracrine manner. In addition to the systemic effect of PTH-rP manifested as hypercalcemia, the PTH-rP secreted from the neoplasm could have been a local factor involved in the growth of the tumor.

Animals↗

PubMed2000

Extracellular signal-regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and matrigel invasion.

The low density lipoprotein receptor-related protein (LRP) has been reported to regulate cellular migration. In this study, an antisense RNA expression strategy was used to reduce LRP to undetectable levels in HT 1080 fibrosarcoma cells. The LRP-deficient cells demonstrated increased levels of cell-surface uPAR, higher levels of uPA in conditioned medium, increased migration on vitronectin-coated surfaces, and increased invasion of Matrigel. LRP-deficient cells also demonstrated increased levels of phosphorylated extracellular signal-regulated kinase (ERK) in the absence of exogenous stimulants. Antibodies which block binding of endogenously produced uPA to uPAR reduced ERK phosphorylation and migration of LRP-deficient cells to the levels observed with control cells. Inhibitors of ERK activation, including PD098059 and dominant-negative MEK1, also decreased the migration of LRP-deficient but not control cells. By contrast, constitutively active MEK1 stimulated the migration of control but not LRP-deficient cells. Although Matrigel invasion by LRP-deficient cells was inhibited by the proteinase inhibitor, aprotinin, PD098059 in combination with aprotinin was necessary for an optimal effect. Expression of the VLDL receptor in LRP-deficient cells reversed the changes in cellular migration and invasion. These studies demonstrate that binding of endogenously produced uPA to uPAR may serve as a major determinant of basal levels of activated ERK and, by this mechanism, regulate cellular migration and invasion. By regulating the uPA/uPAR system, LRP may also regulate ERK activation, cellular migration, and invasion.

Aprotinin↗