Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FIBROSARCOMA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed2001

Lefty contributes to the remodeling of extracellular matrix by inhibition of connective tissue growth factor and collagen mRNA expression and increased proteolytic activity in a fibrosarcoma model.

Homeostasis of the extracellular matrix (ECM) of tissues is regulated by controlling deposition and degradation of ECM proteins. The breakdown of ECM is essential in blastocyst implantation and embryonic development, tissue morphogenesis, menstrual shedding, bone formation, tissue resorption after delivery, and tumor growth and invasion. TGF-beta family members are one of the classes of proteins that actively participate in the homeostasis of ECM. Here, we report on the effect of lefty, a novel member of the TGF-beta family, on the homeostasis of extracellular matrix in a fibrosarcoma model. Fibroblastic cells forced to express lefty by retroviral transduction lost their ability to deposit collagen in vivo. This event was associated with down-regulation of the steady-state level of connective tissue growth factor that induces collagen type I mRNA. In addition, lefty transduction significantly decreased collagen type I mRNA expression and simultaneously increased collagenolytic, gelatinolytic, elastolytic, and caseinolytic activities in vivo by the transduced fibroblasts. These findings provide a new insight on the actions of lefty and suggest that this cytokine plays an active role in remodeling of the extracellular matrix in vivo.

Animals↗
PubMed2006

Activity-based protein profiling implicates urokinase activation as a key step in human fibrosarcoma intravasation.

Entry of malignant cells into the vasculature (i.e. intravasation) requires proteolytic remodeling of the extracellular matrix so that tumor cells may pass through the local stroma and penetrate the vessel wall. The circulatory system then provides a means of transporting tumor cells to distant sites where they extravasate and establish metastatic lesions. This study utilizes activity-based protein profiling to compare the active serine hydrolase repertoire in high intravasating (HT-hi/diss) and low intravasating (HT-lo/diss) variants of the human fibrosarcoma HT-1080 cell line to determine which enzyme(s) play a role in intravasation. Activity-based protein profiling revealed multiple serine hydrolases with altered activity between HT-hi/diss and HT-lo/diss cells, with the largest difference being the activity of urokinase-type plasminogen activator (uPA). Levels of inactive uPA zymogen were similar between the two cell variants, but only HT-hi/diss conditioned medium contained active uPA, suggesting that uPA activation may contribute to the enhanced intravasation of HT-hi/diss cells. To analyze the role of uPA activity specifically in the process of intravasation, we grafted cells from the two HT-1080 variants onto the chorioallantoic membrane of chick embryos and measured levels of tumor cell intravasation in the distal chorioallantoic membrane using quantitative human-specific Alu PCR. Inhibition of uPA activity with natural (plasminogen activator inhibitor-1) or synthetic (amiloride) inhibitors diminished HT-hi/diss Matrigel invasion in vitro and intravasation and metastasis in vivo. Additionally, treatment of HT-lo/diss tumors with exogenous active uPA increased the number of intravasated cells in vivo. These results indicate that active uPA promotes tumor cell intravasation and that uPA activation appears to be a key step in tumor progression.

Animals↗
PubMed2004

Genetic analysis of fibrosarcoma of bone, a rare tumour entity closely related to osteosarcoma and malignant fibrous histiocytoma of bone.

Fibrosarcoma (FS) of bone is an extremely rare and genetically uncharacterised malignant tumour arising in the skeleton. On the basis of clinicopathologic features it appears to be closely related to either fibroblastic osteosarcoma (OS) or malignant fibrous histiocytoma (MFH) of bone. In this study, 27 decalcified, paraffin-embedded FS of bone were collected for genetic and immunohistochemical characterisation. Good quality DNA, suitable for genetic analyses, was isolated from nine cases (7 primary tumours, 1 local recurrence, and 1 lung metastasis), which were analysed by comparative genomic hybridisation (CGH) on chromosomes and DNA microarrays. DNA sequence copy number changes were found in five out of seven primary tumours (72%), as well as in both, the local recurrence and the metastatic lesion, by CGH on chromosomes. The most frequent aberration was gain of the chromosomal region 22q, which was present in four out of the five primary tumours with genetic changes, in the local recurrence and, as the sole genetic aberration, in the lung metastasis. DNA microarray analysis showed that gain of the platelet-derived growth factor beta (PDGF-B) gene (located at 22q12.3-q13.1) was the most frequent gene imbalance, which was present in three out of the five analysed tumours. In these three cases, real-time PCR revealed a 2.1- to 2.7-fold increase of PDGF-B gene copy numbers. By immunohistochemistry, a positive reaction for B-chain-containing PDGF proteins was revealed in all the cases showing gain of 22q. A more extensive immunohistochemical analysis identified the presence of PDGF-B proteins in 8/20 primary FS of bone (40%), 3/3 lung metastases and in 1/2 local recurrences. A simultaneous positive reaction for PDGF-B proteins and PDGF receptors was found in two third of PDGF-B-positive cases (8/12). Taken together, the genetic and immunohistochemical data indicate that over-representation of the chromosomal region 22q, including particularly the PDGF-B gene, may be important for the pathogenesis of FS of bone. Our results also demonstrate that CGH on chromosomes and DNA microarrays are suitable for the genetic characterisation of decalcified, paraffin-embedded tumour tissue samples and may facilitate, combined with other techniques, the rapid acquisition of data providing insight into the molecular genetic and biologic basis of rare bone sarcomas. Moreover, these findings suggest the possible presence of an autocrine loop in FS of bone, which might be taken into account for planning innovative therapeutic strategies for patients unresponsive to conventional treatments.

Adult↗
PubMed2003

Cellular mesoblastic nephroma: morphologic, cytogenetic and molecular links with congenital fibrosarcoma.

Congenital mesoblastic nephroma (CMN) is a rare renal tumor of early infancy with a favorable outcome after complete surgical removal. CMN consists of a heterogeneous group of spindle cell tumors subdivided into "classical", "cellular or atypical" and "mixed" forms based on histologic features. We describe a new case of cellular CMN diagnosed by antenatal ultrasonography with complete remission five years after nephrectomy. Cytogenetic study evidenced a trisomy 11, and real time RT-PCR, but not conventional karyotype, allowed for the detection of the Tel-ETV6/TrkC-NTRK3 fusion transcript as a consequence of a cryptic t(12-15)(p13;q25). As in congenital fibrosarcoma (CFS), two Tel-ETV6/ TrkC-NTRK3 fusion transcripts different by a 42 bp insert in the TrkC kinase domain were expressed. Our observations outline the close links between cellular CMN and CFS. Both tumors have the clinical presentation and histologic features as well as identical cytogenetic and molecular markers in common. Therefore, they are likely to represent the same neoplasm, but occurring at different locations.

Chromosome Aberrations↗
PubMed2001

Photodynamic therapy of murine fibrosarcoma with topical and systemic administration of hypericin.

The in vivo antitumour activity of the natural photosensitizer hypericin was evaluated. C3H/DiSn mice inoculated with fibrosarcoma G5:1:13 cells were intraperitoneally or intratumourally injected with hypericin (5 mg/kg) and 2 hours later the mice were locally irradiated with laser light (488 nm, 150 mW/cm2, 180 J/cm2) when the tumour reached volume of 40-80 mm3 (approximately 17 days after inoculation). Tumours treated with hypericin alone as well as those irradiated with laser light alone have similar growth rates and none of these tumours regressed spontaneously. The mean tumour volume in hypericin-PDT treated groups was significantly lower in comparison to that found in the control group 3-5 weeks after the therapy. A higher proportion of animals with tumour volume less than 5-fold of the initial volume has been observed in both hypericin-PDT treated groups. Complete response to PDT has been observed for 44.4% of the animals with intraperitoneally administered hypericin and for 33.3% of the animals with intratumourally administered hypericin. Complete remission occurred in treated lesions with 3 mm or less in height. Hypericin-PDT significantly increased survival. However, no statistically significant difference in survival rate of animals has been found between the intratumoural and the intraperitoneal schedule of administration of hypericin.

Animals↗
PubMed1997

DHA feeding provides host protection and prevents fibrosarcoma-induced hyperlipidemia while maintaining the tumor response to araC in Fischer 344 rats.

Fischer 344 rats were inoculated with fibrosarcoma tumor cells and fed diets containing 5% or 10% (wt/wt) safflower oil or 10% oil containing docosahexaenoic acid (DHA). Animals were then treated with arabinosylcytosine (araC) or saline for six days. Tumor weights were highest in animals fed 10% safflower oil and treated with saline, intermediate in animals fed oil containing DHA and 5% safflower oil and treated with saline, and lowest in araC-treated animals from all diets. Plasma cholesterol and triglyceride levels correlated highly with final tumor size, regardless of diet or treatment group. Animals fed safflower oil had lower intestinal weights than those fed DHA, which histology demonstrated to be a result of differences in villus height and crypt depth. Substantial loss of bone marrow cells occurred in all dietary groups treated with araC; however, the proportion of granulocyte-macrophage precursors remaining in the DHA animals was higher than in saline-treated animals and twofold higher than in the animals fed 10% safflower oil and treated with araC. These data suggest that, even in the face of rapid tumor growth and chemotherapeutic challenge, consumption of a diet rich in DHA can slow tumor growth, prevent hyperlipidemia, enhance bone marrow cellularity, and promote intestinal growth compared with a moderate-fat n--6-rich diet.

Animals↗
PubMedDate not supplied

Effect of whole body hyperthermia on radiation therapy of transplanted fibrosarcoma in Swiss mice.

The exposure of normal mice to whole body hyperthermia (1 h WBH at 39 or 40 degrees C), 20 or 48 h prior to total body irradiation (TBI) with lethal doses of gamma-rays affords significant protection as assessed by survival. The radioprotective effect of WBH, as observed in normal mice, diminished in tumour bearing mice depending upon the size of tumour. Treatment of tumour bearing mice with mild WBH, 20 h prior to local irrradiation (LIR), did not protect the transplanted tumour against radiotherapy with a single dose of 20 Gy or fractionated dose (in five fractions) of 7.5 Gy on alternate days. In fact, mild WBH treatment enhanced the tumour regression and increased the mean survival time after fractionated dose therapy. However, the prior mild WBH was found to be ineffective in protecting normal tissue, as assessed by skin contraction after local irradiation (50 Gy). This indicates that mild WBH treatment given 20 h prior to local radiotherapy enhances fibrosarcoma tumour regression but cannot protect skin (normal tissue) against local irradiation. It appears that radioprotection of animals by WBH may be the consequence of its radioprotective effect on haemopoietic tissues mediated through certain cytokines. Perhaps WBH may not have a radioprotective effect on other tissues, as evident from skin contraction studies.

Animals↗
PubMedDate not supplied

Effects of cell damage and glycosaminoglycan degradation on available extravascular space of different dextrans in a rat fibrosarcoma.

Drug delivery to solid tumors may be enhanced through increasing the available volume fraction (K(AV)) of drugs. Therefore, two approaches were investigated that may increase K(AV) of dextrans in a rat fibrosarcoma: (a) damaging cells in tumours via ex vivo incubation of tumour tissues, and (b) degrading tumour glycosaminoglycans (GAGs) with exogenous hyaluronidase. The molecular weights of dextrans used in this study were approximately 10,000 (D10), 70,000 (D70) and 2,000,000 (D2000), respectively. It was found that GAG degradation had minimal effects on K(AV) of dextrans. Ex vivo incubation at 37 degrees C for up to 3 h caused only minor cell damage and had minimal effects on K(AV) of D10 and D70. However, the ex vivo incubation reduced K(AV) of D2000 (p < 0.05). When the incubation at 37 degrees C was maintained for 20 h, the amount of viable cells in tumours was reduced by 56% and K(AV) of all dextrans were significantly increased (p < 0.05). Ex vivo incubation at 41 degrees C for 3 h caused similar cell damage to that at 37 degrees C for 20 h, but only K(AV) of D10 and D70 were increased significantly (p < 0.05). There was no significant change in K(AV) of D2000, although it was higher than that in tumours incubated at 37 degrees C for 3 h (p < 0.05). These data suggest that cell damage is a more effective approach than GAG degradation for increasing K(AV) of macromolecules and that the amount of increase depends on the degree of cell damage and the size of molecules.

Animals↗
PubMed1999

Infantile fibrosarcoma. Report of two cases.

We present two cases of infantile fibrosarcoma, one of which was thought to be a congenital tumour on the thigh and was initially diagnosed as a haemangioma, and the other was a tumour on the trunk. Although both recurred locally after initial surgical treatment, wide local re-excision controlled the disease without adjuvant treatment.

Female↗
PubMed1992

Linear quadratic model of radiocurability on multicellular spheroids of human lung adenocarcinoma LCT1 and mouse fibrosarcoma FSA.

The LCT1 cells derived from a human lung adenocarcinoma and the FSA cells from a mouse fibrosarcoma were found to form spheroids. The cure-dose relationship of spheroids and the survival curves of their component cells were analysed by using a linear-quadratic model for cell survival and a Poisson distribution for cure. The analysis resulted in three conclusions: (1) the double minus logarithm of cure probability was linearly related to radiation dose, (2) the critical cell number was constant at any given cure probability, and (3) cellular radiosensitivity was also constant. The experiments seem to meet these conditions for each of two kinds of spheroids. Control doses (50%) were 20 Gy for LCT1 spheroids and 21 Gy for FSA spheroids, both 400 microns in diameter. The analysis showed that the lower cellular radiosensitivity and the higher number of clonogenic cells made LCT1 spheroids more radioresistant than FSA spheroids and that the higher critical number of 130 cells made the LCT1 spheroids more sensitive than the FSA spheroids with 18 such cells. The overall radiocurability of spheroids was a result of these three opposing effects, indicating that the critical cell number can be one important factor in determining the radiocurability of multicellular systems.

Adenocarcinoma↗
PubMed1992

Oncogenes in X-ray-transformed C3H 10T1/2 mouse cells and in X-ray-induced mouse fibrosarcoma (RIF-1) cells.

In order to better understand the molecular basis of X-ray induced carcinogenesis we have investigated RNA levels of oncogenes in an X-ray transformed C3H 10T1/2 fibroblast line (XTD) and RIF-1 cells isolated from an X-ray-induced fibrosarcoma in a C3H mouse. Steady-state levels of K-ras, H-ras, N-ras, abl, sis, src, and fos were unchanged in the X-ray-transformed cells compared with non-transformed C3H 10T1/2 cells. However, myc and raf mRNA levels were increased dramatically in the transformed cells. Data further suggests a possible alteration in processing of raf RNA in the XTD cells. Southern blot analysis of secondary transfectants induced with XTD DNA indicated that the oncogenic phenotype did not segregate with the myc or raf loci; nor with nine other oncogenes analysed.

Animals↗
PubMed1999

Accelerated reoxygenation of a murine fibrosarcoma after carbon-ion radiation.

PURPOSE: Reoxygenation of a murine tumour after irradiation with carbon ions was investigated and compared to that after gamma-rays. MATERIALS AND METHODS: NFSa fibrosarcoma cells were transplanted into the right hind legs of syngeneic C3H male mice. Conditioning irradiation with either 290 MeV/u carbon ions or 137-Cs gamma-rays was delivered to the tumours at 8 mm diameter. At given times after irradiation the leg tumours, either clamped or not, received test doses of photons. Differences in tumour growth delay between the clamped and non-clamped tumours were interpreted in terms of reoxygenation. A lung-colony assay was used to obtain cell-survival curves. RESULTS: The oxygen enhancement ratio in the NFSa tumour for 74 keV microm(-1) carbon ions was 1.6 while that for gamma-rays was 3.4. The NFSa tumours reoxygenated 4 days after 30 Gy of gamma-ray irradiation, but reoxygenated as early as 1 day after 16 Gy of carbon ions. Reoxygenation after gamma-rays shortened to 1 day when the tumours were initially clamped for the conditioning irradiation. CONCLUSIONS: The fraction of surviving oxic cells in the NFSa tumours is larger after irradiation with carbon ions than with gamma-rays, resulting in accelerated reoxygenation.

Animals↗
PubMed1987

Enhancement of pulmonary metastasis of murine fibrosarcoma NR-FS by ozone exposure.

The effects of ozone exposure on the metastasis of a fibrosarcoma (NR-FS) that arose spontaneously in a C3H/He mouse was studied. Male C3H/He mice were exposed to 0.8, 0.4, 0.2, and 0.1 ppm ozone for 1, 3, 5, 7, and 14 d. After the exposure periods, the mice were infused intravenously with NR-FS cells. At 2 wk postinfusion, the lungs were examined for colony development of metastasis. A significantly higher rate of pulmonary metastasis than that of normal mice was observed in the ozone-exposed mice. The enhancement of metastasis due to ozone exposure varied with length of exposure and concentration of ozone. When 1 X 10(5) cells of NR-FS were injected into the tail veins of mice, the maximal enhancement (459%) of pulmonary metastasis was observed in the mice exposed to 0.8 ppm ozone for 1 d. A longer period of exposure to 0.8 ppm ozone also enhanced pulmonary metastasis, although the prolonged exposure (14 d) gradually suppressed the enhancement (268%). In the mice exposed to the lower concentration of ozone, a lower rate of the lung matastasis was observed; even in the mice exposed to 0.1 ppm ozone for the period of from 1 to 14 d, a significantly higher rate of metastasis than that of nonexposed mice was observed.

Administration, Inhalation↗
PubMed1987

Infantile fibrosarcoma of femur.

We describe the clinical presentation and pathological features of an infantile fibrosarcoma of the femur that occurred in a 3 1/2-month-old male infant. The tumor grew rapidly, reaching large size within a few months, finally requiring amputation. The tumor was poorly circumscribed, infiltrating the adjacent soft tissue extensively. Microscopically, it was a highly cellular tumor composed of immature-appearing spindle-shaped cells. Ultrastructural study revealed mesenchymal cells with fibroblastic and histiocytic differentiation.

Bone Neoplasms↗
PubMed1988

Spinal cord compression by epidural metastases. Fibrosarcoma experiments in rats.

Morphologic changes were studied in 43 rats that were paralyzed by an epidural fibrosarcoma inoculated through the spinous process. By this technique, of 29 rats examined radiographically, the tumor destroyed vertebral bone in 22. Changes of the cord in the early stage of paralysis were specially analyzed by Marchi's stain and microangiograms. In compromised cord segments in the early stage, extravasation of contrast medium was observed in the gray matter and the dorsal funiculus; and in the dorsal funiculus just proximal or distal to the compressed portion, hemorrhagic areas were present. Ascending degenerated fibers in the dorsal funiculus, which were derived from the degenerated posterior nerve root or the degeneration of the dorsal funiculus in the compressed segments, were characteristically detected in rats in the early stages. In the advanced stages a transverse cord lesion was observed at the involved level. Based on the present analyses, to prevent more advanced damage to the spinal cord, the tumor should be removed at an early stage that clinically coincides with the period when radicular signs appear.

Animals↗
PubMed2003

Local delivery of IL-1 alpha polymeric microspheres for the immunotherapy of an experimental fibrosarcoma.

The immunotherapeutic effects of interleukin-1 alpha (IL-1 alpha) encapsulated within 1-5 microns-diameter poly (D, L-lactide) microspheres and delivered intratumorally into fibrosarcoma-bearing mice were investigated. Such microspheres are avidly taken up by macrophages, and directing IL-1 alpha into these cells may activate them to participate in antitumor responses in vivo. Treating of tumor-bearing mice with IL-1 alpha microspheres has increased their survival rate, as compared with control mice, untreated or treated with microspheres containing bovine serum albumin (BSA). In 20% of the IL-1 alpha-treated mice, a complete tumor regression was observed. The timing of treatment with IL-1 alpha microspheres was crucial; optimal survival and regression rates were observed in mice treated 24 hr postinjection of the tumor cells. Administration of three doses of IL-1 alpha microspheres on days 1, 8, and 15 postinjection of tumor cells resulted in longer survival rates. Histopathology studies on regressed tumors revealed extensive areas of tumor cell degeneration and necrotic tissue surrounded by a large number of inflammatory cells. A similar picture was observed when IL-1 alpha microspheres were administered into the footpad of control mice, whereas the tissue reaction to BSA microspheres was much milder. Thus, it appears that tumor regression is mainly due to the antitumor effects of IL-1 alpha. Further studies are being aimed at increasing the immunotherapeutic efficiency of microspheric IL-1 alpha, used as a single treatment or in combination with other treatment modalities.

Animals↗
PubMed1985

Uptake and subcellular distribution of [3H]arachidonic acid in murine fibrosarcoma cells measured by electron microscope autoradiography.

We have used quantitative electron microscope autoradiography to study uptake and distribution of arachidonate in HSDM1C1 murine fibrosarcoma cells and in EPU-1B, a mutant HSDM1C1 line defective in high affinity arachidonate uptake. Cells were labeled with [3H]arachidonate for 15 min, 40 min, 2 h, or 24 h. Label was found almost exclusively in cellular phospholipids; 92-96% of incorporated radioactivity was retained in cells during fixation and tissue processing. All incorporated radioactivity was found to be associated with cellular membranes. Endoplasmic reticulum (ER) contained the bulk of [3H]arachidonate at all time points in both cell types, while mitochondria, which contain a large portion of cellular membrane, were labeled slowly and to substantially lower specific activity. Plasma membrane (PM) also labeled slowly, achieving a specific activity only one-sixth that of ER at 15 min in HSDM1C1 cells (6% of total label) and one-third of ER in EPU-1B (10% of total label). Nuclear membrane (NM) exhibited the highest specific activity of labeling at 15 min in HSDM1C1 cells (twice that of ER) but was not preferentially labeled in the mutant. Over 24 h, PM label intensity increased to that of ER in both cell lines. However, NM activity diminished in HSDM1C1 cells by 24 h to a small fraction of that in ER. In response to agonists, HSDM1C1 cells release labeled arachidonate for eicosanoid synthesis most readily when they have been labeled for short times. Our results therefore suggest that NM and ER, sites of cyclooxygenase in murine fibroblasts, are probably sources for release of [3H]arachidonate, whereas PM and mitochondria are unlikely to be major sources of eicosanoid precursors.

Animals↗
PubMed1987

Induction of fibronectin matrix assembly in human fibrosarcoma cells by dexamethasone.

Previous studies have suggested that the assembly of fibronectin into the extracellular matrix of cultured fibroblasts is mediated by specific matrix assembly receptors that recognize a binding site in the amino terminus of the fibronectin molecule (McKeown-Longo, P.J., and D.F. Mosher, 1985, J. Cell Biol., 100:364-374). In the presence of dexamethasone, human fibrosarcoma cells (HT-1080) acquired the ability to specifically bind exogenous plasma fibronectin and incorporate it into a detergent-insoluble extracellular matrix. Dexamethasone-induced fibronectin binding to HT-1080 cells was time dependent, dose dependent, and inhibited by cycloheximide. Saturation binding curves indicated that dexamethasone induced the appearance of 7.7 X 10(4) matrix assembly receptors per cell. The induced receptors exhibited a dissociation constant (KD) for soluble fibronectin of 5.0 X 10(-8) M. In parallel experiments, normal fibroblasts exhibited 4.1 X 10(5) receptors (KD = 5.3 X 10(-8) M) per cell. In the presence of cycloheximide, the induced fibronectin-binding activity on HT-1080 cells returned to uninduced levels within 12 h. In contrast, fibronectin-binding activity on normal fibroblasts was stable in the presence of cycloheximide for up to 54 h. The first-order rate constant (Kt = 2.07 X 10(-4) min-1) for the transfer of receptor-bound fibronectin to extracellular matrix was four- to fivefold less than that for normal fibroblasts (Kt = 1.32 X 10(-3) min-1). Lactoperoxidase-catalyzed iodination of HT-1080 monolayers indicated that a 48,000-mol-wt cell surface protein was enhanced with dexamethasone. The results from these experiments suggest that dexamethasone induces functional matrix assembly receptors on the surface of HT-1080 cells; however, the rate of incorporation of fibronectin into the matrix is much slower than that of normal fibroblasts.

Cell Membrane↗