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At least 631 records · Page 35Linked to original sources
PubMed1995

Composition of ether-linked sub-classes of glycerophospholipids in clones with a different metastatic potential isolated from a murine fibrosarcoma line (T3 cells).

An increase of ether-linked sub-classes of choline and ethanolamine glycerophospholipids has been shown in different types of tumor cells, and correlated with some of their specific biological parameters. In the present study, we examined the composition of ether-linked lipids in a series of clones with a different lung-colonizing potential isolated in our laboratory from a highly metastatic fibrosarcoma line (T3 cells). We found good correlation between the metastatic potential of T3 isolates and increased proportions of both alkylacyl and alkenylacyl subclasses in choline glycerophospholipids (CGP). Moreover, propagation of a weakly metastatic T3 clone in tissue culture led to the emergence of a sub-clone which expressed high metastatic potential together with a high level of alkylacyl and alkenylacyl CGP. No differences were found in the alkylacyl and alkenylacyl-ethanolamine glycerophospholipids (EGP) between the strongly and weakly metastatic T3 clones. We discuss the accumulation of alkylacyl and alkenylacyl CGP in metastatic cells for its possible role in metastatic diffusion by generation of platelet-activating factor (PAF).

Animals↗
PubMed1984

Mechanism of activation of an N-ras gene in the human fibrosarcoma cell line HT1080.

A full length N-ras gene has been cloned from both the human fibrosarcoma cell line HT1080 and from normal human DNA. N-ras isolated from HT1080 will efficiently induce morphological transformation of NIH/3T3 cells in a transfection assay, whereas N-ras isolated from normal human DNA has no effect on NIH/3T3 cells. The coding regions of the normal N-ras gene have been sequenced and the predicted amino acid sequence of the N-ras product is very similar to that of the c-Ha-ras1 and c-Ki-ras2 products. By making chimeric molecules between the two cloned genes the activating alteration in the HT1080 N-ras gene has been localised to a single base change that results in an amino acid alteration at position 61 of the p21 N-ras product.

Amino Acid Sequence↗
PubMed1986

Suppression of urokinase-type plasminogen activator mRNA levels in human fibrosarcoma cells and synovial fibroblasts by anti-inflammatory glucocorticoids.

Suppression of plasminogen activator (PA) activity has been invoked as being part of the general anti-inflammatory action of glucocorticoids. Low concentrations of the synthetic glucocorticoid, dexamethasone (Dex), reduce urokinase-type PA mRNA levels in two cell types, namely a human fibrosarcoma line, HT1080, and synovial fibroblast-like cells isolated from human joints. Conversely, metallothionein IIa (MTIIa) mRNA levels in these cells are raised by Dex. These findings, by suggesting that it is possible to suppress urokinase-type PA activity at the level of gene expression, may have therapeutic implications for diseases such as rheumatoid arthritis where proteases may be contributing to the extensive tissue damage and inflammation.

Cell Line↗
PubMed2005

Arsenic trioxide (As2O3) inhibits invasion of HT1080 human fibrosarcoma cells: role of nuclear factor-kappaB and reactive oxygen species.

In order to define the role of As2O3 in regulating the tumor cell invasiveness, the effects of As2O3 on secretion of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA), and in vitro invasion of HT1080 human fibrosarcoma cells were examined. As2O3 inhibited cell adhesion to the collagen matrix in a concentration dependent manner, whereas the same treatment enhanced cell to cell interaction. In addition, As2O3 inhibited migration and invasion of HT1080 cells stimulated with phorbol 12-myristate 13-aceate (PMA), and suppressed the expression of MMP-2, -9, membrane type-1 MMP, uPA, and uPA receptor (uPAR). In contrast, As2O3 increased the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and PA inhibitor (PAI)-1, and reduced the MMP-2, -9, and uPA promoter activity in the presence and absence of PMA. Furthermore, the promoter stimulating and DNA binding activity of nuclear factor-kappaB (NF-kappaB) was blocked by As2O3, whereas the activator protein-1 activity was unchanged. Pretreatment of the cells with N-acetyl-L-cysteine (NAC) significantly prevented suppression of MMPs and uPA secretion, DNA binding activity of NF-kappaB, and in vitro invasion of HT1080 cells by As2O3, suggesting a role of reactive oxygen species (ROS) in this process. These results suggest that As2O3 inhibits tumor cell invasion by modulating the MMPs/TIMPs and uPA/uPAR/PAI systems of extracellular matrix (ECM) degradation. In addition, the generation of ROS and subsequent suppression of NF-kappaB activity by As2O3 might partly be responsible for the phenomena. Overall, As2O3 shows potent activity controlling tumor cell invasiveness in vitro.

Apoptosis↗
PubMed1977

Studies on a fractionated murine fibrosarcoma: a reproducible method for the cautious and a caution for the unwary.

A technique is described for the dissociation and fractionation by isopycnic centrifugation (4,000 x g, 60 minutes, 4 degrees C) in linear bovine albumin density gradients (12 ml, pH 5.2 real osmolality 333 mmol/Kg water, 1.030-1.075 g/cm3) of cells ( less than or equal to 3 x 10(7)/gradient) released by a strictly standardised combination of mechanical and enzymatic means from a transplantable methylcholanthrene induced BALB/c fibrosarcoma. Optimal conditions for reproducible localisation of cell bands with maintenance of both satisfactory resolution and satisfactory viable cell recovery ( greater than 80%) were established by means of a series of simultaneous double fractionation experiments. When rebanding was performed under these conditions the density of the median of the cell count of the refractioned cells shifted less than 0.0005 g/cm3. Experiments also showed that close adherence to certain aspects of the tissue dissociation and fractionation protocol was necessary to avoid reduced cell yields and viabilities, density-dependent selective cell lossses, reductions in resolution and shifts in the location of cell bands. Other aspects of the protocol were tolerant to variation without introducting artefacts.

Animals↗
PubMed1987

Intraclonal diversity of fibrosarcoma cells for the production of macrophage colony-stimulating factor and granulocyte colony-stimulating factor.

A new cell line was established from fibrosarcoma that had spontaneously developed in a mouse. The cells were maintained growing in culture for two years and constantly produced both macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF). Cloning of the cells by anchorage-independent colony formation gave subclones showing the activity of producing M-CSF and G-CSF in different proportions, whereas no subclone produced G-CSF without producing M-CSF simultaneously. Recloning of the bipotential subclones again gave clonal derivatives producing two types of CSF in various proportions. The observed heterogeneity of the cloned cells seems to be an epigenetic phenomenon, because the cells resumed the G-CSF producing activity in the absence of cell proliferation. After equilibrium was achieved, all of the subclones produced both M-CSF and G-CSF nearly in equal proportions. Tumorigenic and leukocytosis-inducing activity of the cloned cells was nearly comparable with the activity of the original tumor cells.

Animals↗
PubMed1995

Release from quiescence stimulates the expression of integrin alpha 5 beta 1 which regulates DNA synthesis in human fibrosarcoma HT1080 cells.

We show that integrin alpha 5 subunit expression is stimulated when human fibrosarcoma HT1080 cells are released from quiescence. The alpha 5 subunit mRNA level in quiescent HT1080 cells was increased 24 hr after their release by 10% fetal bovine serum-containing medium reaching a maximum of 2.5 fold on day 2. Similar levels of induction of cell-surface alpha 5 subunit protein as well as beta 1 subunit protein were also observed. This resulted in a significant increase of cell attachment to fibronectin. The serum stimulation also increased alpha 5 subunit promoter activity by twofold which was protein synthesis independent. Subsequent deletion of alpha 5 subunit promoter DNA showed that the cis-element responsible for the activation is located between -92 bp and the transcription start site. The promoter activity was not induced until 12 hr after the release. Comparison of the effect of a serum-free medium and a 10% fetal bovine serum-supplemented medium revealed that both the DNA synthesis and alpha 5 subunit induction were independent of exogenous growth factors. The increased integrin alpha 5 beta 1 appears to function by reducing mitogenic activity since blockade of fibronectin binding to its receptor with a RGD peptide, a monoclonal anti-fibronectin antibody, or a monoclonal anti-alpha 5 subunit antibody during the release from quiescence significantly stimulated DNA synthesis. On the other hand, stable overexpression of the alpha 5 subunit resulted in decreased DNA synthesis.

Cell Adhesion↗
PubMed1977

Chemoimmunotherapy of a murine fibrosarcoma: critical factors for success of combined modality therapy.

Thiabendazole (TBZ), a new nonspecific immunopotentiator, was evaluated in combination with Cytoxan in the therapy of a syngeneic murine fibrosarcoma. The reduction of tumor burden by chemotherapy was critical in achieving an optimal response from immunotherapy. Eighty-eight percent of the mice that responded to Cytoxan had sustained regression of tumor with TBZ treatment. The response to TBZ was markedly diminished, both in duration and magnitude, in the mice considered to be Cytoxan nonresponders. Timing of immunotherapy was also important. If Cytoxan and TBZ were given simultaneously, growth kinetics similar to those observed with Cytoxan alone were observed. However, if TBZ was given 4 days after Cytozan administration, prolonged regression of tumor was seen. Alone, TBZ was most effective at a dose of 20 mg/kg. However, in combination with Cytoxan the most effective dose was 0.2 mg/kg. The implications of this finding are discussed.

Animals↗
PubMed1977

The combined effect of radiotherapy and neuraminidase-treated tumor cells on 3-methylcholanthrene-induced fibrosarcoma.

Active immunotherapy with tumor cells treated in vitro with Vibrio cholerae neuraminidase (VCN) plus mitomycin C augments the antitumor effects of local x irradiation in the treatment of firmly established methylcholanthrene-induced fibrosarcoma, MC-43, in syngeneic C3H/HeJ female mice. In most experiments, the inhibition of tumor growth was greater when VCN-treated tumor cells were combined with local irradiation than could be achieved with VCN-treated tumor cells or local irradiation alone. Even in those experiments in which the immunotherapeutic effect of VCN-treated cells was negligible, the combination of radiotherapy and immunotherapy appeared to be greater than irradiation alone. Similarly, total permanent regression of established tumors occurred more frequently after combined therapy than after immunotherapy or radiation therapy alone.

Animals↗
PubMed1979

Fibrosarcoma of the mediastinum.

Fibrosarcoma is a rare primary malignant tumor of the mediastinum. Three cases are presented with different presenting symptoms and clinical manifestations. Thoracotomy with biopsy of the mass is the only method for arriving at a definitive histologic diagnosis.

Adult↗
PubMed1984

The effect of immunity on pulmonary metastasis of a methylcholanthrene-induced fibrosarcoma and three of its clones.

A 3-Methylcholanthrene (MC)-induced fibrosarcoma and three of its clones were investigated for their metastatic potential in normal and tumor immune mice. The growth rates of the four tumors in vivo were similar. However, the mean survival times of the tumor-bearing mice were markedly different. Clone 10, the most immunogenic, showed very high metastatic potential and short survival, while clone 27, the least immunogenic, produced few metastases, resulting in much longer survival. Moderate numbers of metastases were produced by highly immunogenic 3-AM (parental tumor), and poorly immunogenic clone 34. Spleen cells from mice bearing highly immunogenic tumors lost their ability to neutralize tumors by day 28 after tumor inoculation, while those from mice bearing poorly immunogenic tumors remained cytotoxic, indicating that highly immunogenic tumors also induced immune suppression in the hosts. Immunization with specific tumors decreased the number of pulmonary metastases by 3 to 35-fold. Immunization with tumors that shared antigens provided protection against metastatic tumors as well as the local tumors. In contrast, immunization with antigenically different tumors gave no protection.

Animals↗
PubMed1985

Therapeutic advantage in preoperative single-dose radiation combined with conservative and radical surgery in different-size murine fibrosarcomas.

The efficacy of surgery alone or combined with preoperative radiation was examined using isotransplants of the spontaneous fibrosarcoma (FSaII) growing in the right leg of syngeneic C3Hf/Sed mice and employing as end-points both local tumor control probability and normal tissue damage. Complete assays have been performed on small (4-5 mm) and large (8 mm) tumors. The TCD50s (the dose required to control half the irradiated tumors) for radiation alone were 63.2 and 82.7 Gy for small and large tumors, respectively. Surgery was performed 4 days after the radiation treatment. Surgical resections were performed under an 8 X dissecting microscope. In small tumors, radical (enbloc resection) and conservative (local resection) surgery alone achieved 69.8% (30/43) and 21.9% (7/32) tumor control. The corresponding figures for large tumor were 25% (8/32) and 6.1% (2/33), respectively. The combination of radiation and surgery increased tumor control frequency up to 100% with doses lower than TCD50 for radiation alone. The TGF is expressed as therapeutic gain factor for conservative and for radical surgery for 4-5-mm and for 8-mm tumors from analyses of dose response curves for tumor control and leg shortening. In small tumors, the TGFs at the 80% tumor control (TCD80) and leg shortening of 5 mm were 1.4 and 1.8 for radical and conservative resection, respectively. The TGFs at the TCD50 level for large tumors were 1.4 and 1.7 in respective resections. In this particular experimental system, conservative surgery yielded higher TGFs than radical surgery for both tumor sizes. No effect of preoperative treatment on the frequency of distant metastasis was observed.

Amputation, Surgical↗
PubMed1986

Effect of fractionated irradiation prior to conservative and radical surgery on therapeutic gain in a spontaneous fibrosarcoma of the C3H mouse.

The efficacy of fractionated irradiation given preoperatively was examined using early generation isotransplants of a spontaneous fibrosarcoma (FSaII) growing in the right leg of syngeneic C3Hf/Sed mice and employing as endpoints local tumor control probability, normal tissue damage (5 mm leg shortening), and distant metastasis. Complete dose response assays have been performed on small (4-5 mm) and large (8 mm) tumors. TCD50s (the dose that on average would be expected to control half the irradiated tumors) for radiation given in five equal doses (1 day between treatments) were 93.6 and 111.8 Gy for the 4-5 and 8-mm tumors, respectively. Surgery was performed under a dissecting (8X) microscope at 5-6 days after the completion of irradiation. For small tumors, radical (en bloc) and conservative (local) resection alone achieved 69.8 (30/43) and 21.9% (7/32) tumor control, respectively. The corresponding figures for large tumors were 25 (8/32) and 6.1% (2/33), respectively. Preoperative irradiation increased tumor control rate up to 100% at dose levels much lower than TCD50 for radiation alone. Enhancement ratios (ER) were computed for preoperative radiation as follows: TCD50 for radiation alone/TCD50 for radiation and surgery. ERs were computed for local and en bloc resection for tumor control and for leg shortening. From these ER values, therapeutic gain factors (TGF) were then computed for local and en bloc resection for tumor control and for leg shortening. From these ER values, therapeutic gain factors (TGF) were then computed as ER tumor response/ER leg shortening. In small tumors, the TGFs (TCD80 and leg shortening of 5 mm) were 2.1 and 2.0 for conservative and radical resection, respectively. Corresponding figures for large tumors were 1.5 and 1.5. In this experimental system for small and large tumors, radiation treatment prior to conservative surgery achieved a comparable therapeutic gain to that by combining radiation with radical surgery. No effect of preoperative fractionation on the frequency of distant metastasis was observed.

Animals↗
PubMed1992

Therapeutic gain of local and radical resection combined with postoperative radiation for murine fibrosarcomas.

Resection of 8-mm fibrosarcomas (FSaII) growing in the right leg of syngeneic C3H/Sed mice was performed under a dissecting (x8) microscope. Local and radical resection achieved 20% (5/25) and 48% (12/25) tumor control, respectively. TCD80s (average dose expected to control 80% of irradiated tumors) for radiation alone given as one fraction per day for 5 consecutive days were 73.1 and 118.0 Gy for the microscopic and 8-mm tumors, respectively. Radiation therapy started at 4 or 7 days following local or radical resection enhanced both the local tumor control and the treatment-related morbidity represented by leg shortening. From enhancement ratios (ERs) for tumor control (TCD80 for radiation alone/TCD80 for postoperative radiation) and for leg shortening (dose for 5-mm leg shortening for radiation alone/postoperative radiation) values, therapeutic gain factors (TGFs) were derived as ER tumor/ER leg shortening. These were 1.3 and 1.4 for local and radical resection followed by radiation started on the 7th postoperative day, respectively. Corresponding figures for radiation started on the 4th postoperative day resulted in 1.2 for both resection procedures.

Animals↗
PubMed2002

Inducible expression of the gap junction protein connexin43 decreases the neoplastic potential of HT-1080 human fibrosarcoma cells in vitro and in vivo.

Numerous studies have demonstrated a correlation between dysregulation/loss of connexin expression or gap junction intercellular communication (GJIC) function and decreased growth control both in human tumors and tumor cell lines. Likewise, restoration of constitutive connexin expression/function is correlated with increased growth control/decreased tumorigenicity. Here, we show for the first time that inducible restoration of connexin43 (Cx43) expression and GJIC function in a human tumor line of mesenchymal origin (HT-1080, fibrosarcoma) resulted in a lowered neoplastic potential. Specifically, HT-1080 cells induced to express Cx43 demonstrated diminished foci formation when in co-culture with normal fibroblasts, decreased colony formation under anchorage-independent conditions, and reduced tumor growth when injected into immunodeficient mice. These results, obtained utilizing an inducible system that helps address issues of clonal heterogeneity, strongly implicate Cx43 as a tumor suppressor in human tissue of mesenchymal origin and GJIC as a regulatory mechanism for cellular growth control both in vitro and in vivo. This study also further supports the hypothesis that loss of Cx43/GJIC in human tumors may play an important role in the dysregulation of normal growth control.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1990

Poor prognosis infantile fibrosarcoma with pathologic features of malignant fibrous histiocytoma after local recurrence.

In a retrospective study of infants under 1 year of age treated at our institution over a 30-year period for soft tissue tumors, eight fibrosarcomas (FS) were seen, six of which were congenital. Therapy consisted of local excision (n = 3), radiotherapy (n = 1), surgery + radiotherapy (n = 1), surgery + chemotherapy (n = 1), and surgery + chemotherapy + radiotherapy (n = 2). Among these eight patients, four are alive in first complete remission (CR) with 13, 17, 23, and 27 years of follow-up. Of the remaining four patients, two had local recurrences and are still alive in CR after re-excision of the tumor, while the other two had both local and distant relapses and died. Interestingly, in the two patients who developed distant metastases, the pathologic pattern was that of malignant fibrous histiocytoma (MFH) at the time of local recurrence. To our knowledge, no similar cases of transitions between infantile FS known for its favorable outcome and MFH have been reported in this age group. The relevance of such transitions is difficult to assess. However, given the known metastatic potential of MFH, we believe that chemotherapy regimens currently used in the management of childhood soft tissue sarcomas should be used in similar cases.

Child, Preschool↗
PubMed1996

Tumor 31P NMR pH measurements in vivo: a comparison of inorganic phosphate and intracellular 2-deoxyglucose-6-phosphate as pHnmr indicators in murine radiation-induced fibrosarcoma-1.

Uncertainty regarding the intracellular/extracellular distribution of inorganic phosphate (P(i)) in tumors has raised concerns that pH calculated from the tumor P(i) chemical shift may not accurately represent the intracellular pH (pHin). This issue was addressed in subcutaneously transplanted murine radiation induced fibrosarcoma-1 by directly comparing pH measured via P(i) with pH measured via the in situ generated intracellular xenometabolite 2-deoxyglucose-6-phosphate (2DG6P). In 131 comparative measurements employing eight tumor-bearing mice under both control and hyperglycemic conditions (the latter to extend the range of tumor pH examined), the pH as derived from either 2DG6P or P(i) showed only a small, but statistically significant, difference (0.07 +/- 0.11 SD; P = 0.0001). Scatter in the comparative analysis over the pH range examined (ca. 5.5-7.5) was not uniform. Above pH 6.6, 2DG6P indicated a pH lower than that of P(i) by 0.088 +/- 0.105 SD (n = 107, P = 0.0001); below pH 6.6, 2DG6P indicated a pH essentially identical to and not statistically different from that of P(i) (mean difference 0.003 +/- 0.128 SD (n = 24, P = 0.92)). Evidence is presented in support of this differential arising from a systematic measurement error due to peak overlap between 2DG6P and endogenous phosphomonoester species. These results support the use of P(i) as a tumor 31P NMR pHin indicator, at least in RIF-1 tumors under control and hyperglycemic conditions.

Animals↗
PubMed2006

Determination of the maturity and functionality of tumor vasculature by MRI: correlation between BOLD-MRI and DCE-MRI using P792 in experimental fibrosarcoma tumors.

Using hypercapnia and carbogen as functional markers of vessel maturation and function, we compared blood oxygen level-dependent (BOLD) contrast with standard dynamic contrast-enhanced (DCE)-MRI quantitative parameters in murine fibrosarcoma. Our results show that there was no correlation between vessel maturity and contrast-agent uptake rate (K(in) (Trans)) or contrast agent efflux rate (k(ep)). In addition, DCE-MRI provided higher estimates of the fraction of functional tumor compared to BOLD-MRI. The two putative markers of regional vascular density, i.e., the magnitude of BOLD signal change during carbogen challenge (VF) and the fractional plasma volume found by DCE-MRI (V(p)), were only weakly correlated (r(2) = 0.02-0.14). Furthermore, VF showed no correlation with K(in) (Trans). A positive correlation was observed (r(2) = 0.75) between mean tumor VF and k(ep), but only when averaged over the whole tumor (which includes tumor regions completely unperfused by the gadolinium (Gd) contrast agent). This would merely reveal a relationship between perfusion status and the capacity to respond to carbogen breathing. In conclusion, characterizations of tumor microvasculature imaging using BOLD-MRI and DCE-MRI appear to be largely complementary, given the weak correlations between their corresponding derived parameters.

Animals↗