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Successful immunotherapy in a murine metastasizing fibrosarcoma model.

Antigenic differences were demonstrated between the primary murine fibrosarcoma and its metastases. Immunization with irradiated primary tumor cells (TC) protected C57B1/6J mice against subsequent challenge with those cells, but not against challenge with cells from pulmonary metastases (PMC). Mice immunized with irradiated PMC were protected from challenge with those cells, but not against challenge with TC. Mice with fibrosarcomas produced by the injection of 5 X 10(3) cells from the primary tumor were treated by resection of the tumor-bearing limb (Amp), Amp plus cyclophosphamide (Amp + Cy), Amp plus primary TC (Amp + TC), Amp plus primary TC and from its metastatic variant (Amp + TC + PMC), and with combinations of the last two groups with Cy. Although Amp + Cy improved survival, no animal lived 100 days and metastases increased as compared to controls. Immunotherapy significantly improved survival and decreased pulmonary metastases. Antigen combinations from primary and metastatic tumors resulted in significantly better survival than did a single preparation only from TC. Chemotherapy did not enhance the results obtained with immunotherapy and surgery. Immunity conferred in long-term survivors was permanent.

Animals↗

Fibrosarcoma of the transverse colon.

Colonic fibrosarcoma is extremely rare. This is a report of a patient with fibrosarcoma of the transverse colon, manifesting as an obstructive lesion with local perforation and abscess formation.

Colon↗

Human fibrosarcoma cells produce fibronectin-releasing peptides.

A sensitive radioimmunoassay, specific for human fibronectin, was used to measure the ability of certain biologically active polypeptides to release fibronectin from cultured human lung fibroblasts into their culture media. Concentrated, serum-free supernatant from a human fibrosarcoma cell line was fractionated by gel filtration chromatography in the presence of acetic acid. Various polypeptides with molecular weights between 46,000 and 6,000 were tested for their ability to release fibronectin from cells. The column fraction, containing polypeptides with an apparent molecular weight of 10,000, exhibited the ability to rapidly release fibronectin from target cells. The activity could be inhibited by phenylmethyl sulphonylfluoride. Several other hormonal factors, tested in parallel with the column fractions, failed to show this effect. The 10,000 dalton molecular weight polypeptides may represent a family of cellular gene products responsible for maintenance of low levels of surface associated fibronectin in fibrosarcoma cells and thus be related to their infiltrating properties by preventing the formation of the extracellular matrix.

Animals↗

A new hamster fibrosarcoma model for in vitro/in vivo evaluation of cancer chemotherapeutic agents.

A hamster fetal cell clone has been developed for in vitro chemotherapeutic studies as well as in an in vivo fibrosarcoma model system. Highly reproducible quantitative in vitro chemotherapeutic data can be obtained with this cell line within 5 days, and as few as 10(2) cells produce rapidly growing fibrosarcomas when injected subcutaneously into adult hamsters. We found using these cells in vitro that 1-beta-D-arabinofuranosylcytosine (ara-C) can antagonize the effect of 5-azacytidine (aza-C) if given simultaneously or if aza-C treatment is preceded by a 2-hr exposure to ara-c. Using the same cell line as in vivo model for chemotherapy it was also shown that ara-C and cyclocytidine significantly inhibited tumor growth. This hamster cell line may be quite useful as an in vitro/in vivo model system for the study of cancer chemotherapeutic agents.

Ancitabine↗

Chemotherapy in the management of infantile fibrosarcoma.

Infantile fibrosarcoma (IF) has traditionally been treated with surgery, which may have considerable morbidity. Chemotherapy has been suggested in order to reduce the need for extensive surgery. Nine children with histologically confirmed IF who received chemotherapy are described. Six children were treated with chemotherapy initially, two following conservative surgery, and one following recurrence after surgery. All received vincristine (V) and actinomycin D (A), and six received additional drugs including ifosfamide (I), cyclophosphamide (C), adriamycin (Ad), etoposide (E), and cisplatinum (CDDP). Objective responses were achieved in eight: three responded completely (CR), two responded partially (PR), which allowed conservative surgery, one had stable disease, one had an initial PR, but subsequently had tumour recurrence 1 month after cessation of treatment, necessitating further surgery and chemotherapy, and one had an initial PR but died following local and regional metastases. One child had no response to chemotherapy but is alive with stable residual disease. Thus, five of nine children achieved a CR--three with chemotherapy alone. With the inclusion of chemotherapy as part of their treatment, five children, for whom curative surgery may have resulted in amputation, remain alive with limbs intact. Chemotherapy including V and A should be given to infants with fibrosarcoma in whom curative surgery would be mutilating.

Antineoplastic Combined Chemotherapy Protocols↗

Dietary curcumin with cisplatin administration modulates tumour marker indices in experimental fibrosarcoma.

Curcumin, the active constituent of Curcuma longa, which itself possesses antitumour activity against experimental tumours, enhances the antitumour effect of the widely used anticancer drug cisplatin, when used in combination against fibrosarcoma. Tumour marker enzymes such as aminotransferases, lactate dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase, 5'-nucleotidase were analysed in liver and kidney homogenates of experimental rats. All these enzyme activities were markedly increased in tumour bearing animals. On cisplatin administration, the enzyme levels were decreased but not to near normal values. Curcumin, when treated along with cisplatin brought back the enzyme levels to near the control values. Thus curcumin and cisplatin combination may be worth trying against tumours like fibrosarcoma.

Analysis of Variance↗

A positive association between agonist-induced cyclic AMP production in vitro and metastatic potential in murine B16 melanoma and hamster fibrosarcoma.

A positive association between agonist-stimulated cyclic AMP production in vitro and both experimentally induced (B16 melanoma) and spontaneous (fibrosarcoma) metastases were found. Five B16 melanoma cell lines producing varying degrees of lung colonization following intravenous injection and three hamster fibrosarcoma cell lines producing a varying number of metastases in lungs and regional lymph nodes after removal of the primary tumour were studied. Agonist-stimulated (forskolin and melanocyte-stimulating hormone), but not basal cyclic AMP accumulation, increased with increasing metastatic potential. This relationship did not extend to other intracellular signalling systems as determined by investigation of basal or foetal-calf stimulated phosphatidylinositol hydrolysis for either tumour type. Intracellular free calcium was also similar in B16 melanoma cell lines of varying metastatic potential.

Animals↗

Fibrosarcoma and malignant fibrous histiocytoma of long bones: radiographic features and grading.

The salient radiological features of 102 cases of fibrosarcoma and of so-called malignant fibrous histiocytoma (MFH) of the long bones are presented. All cases registered with the Netherlands Committee on Bone Tumours in the period 1953-1976, were originally classified as fibrosarcoma. In a recent review of the pathological material approximately half of these tumours were reinterpreted as malignant fibrous histiocytoma. As the two neoplasms demonstrate no difference in their clinical picture, radiological appearance, and survival statistics, we did not study both groups separately. Favourable radiographic signs which suggest a longer survival rate included: a geographic type of bone destruction, eccentric location, and cortical destruction involving no more than two quadrants of the bone circumference. Based on these findings a grading system is presented which differs from that proposed by Lodwick et al. [21].

Adolescent↗

Fibrosarcoma of the jaws.

The records of 14 patients with fibrosarcoma of the jaws--10 in the mandible and four in the maxilla--from the files of the Netherlands Committee on Bone Tumours were studied. The mean age of the patients was 30 years; more men than women were involved; pain and especially swelling were the symptoms most frequently present. The radiographic appearance often indicated the malignant nature of the lesion. Histologically 42% of the tumours were low-grade malignant. The 5-year survival rate was 71%, which is more favourable than either fibrosarcoma located elsewhere in the skeleton or osteosarcoma of the jaws. Radical surgery is the therapy of choice. All cases with an unfavourable course acquired lung metastases.

Adolescent↗

[Fibrosarcoma of the cervical spine. Case report (author's transl)].

Primary malignant tumours of the cervical spine are very rare. Perhaps only 30 reports of sarcoma of the cervical spine have appeared until today. We are recording another case of fibrosarcoma, which was diagnosed initially as hysteric pain in gravidity by a 19-year-old girl. The fibrosarcoma lateron metastasized into the third lumbar vertebra by a direct hematogenic pathway.

Adult↗

Antitumor activity of L-2,4 diaminobuturic acid against mouse fibrosarcoma cells in vitro and in vivo.

Mouse fibrosarcoma cells were grown in vitro and incubated with L-2,4 diaminobuturic acid, a non-metabolizable amino acid. The tumor cells were irreversibly and totally damaged by incubation with 10 mM DAB for 24 h at 37 degrees C. The cell-destructive effect by DAB was probably due to an osmotic lysis induced by the non-saturated intracellular accumulation of DAB. The harmful effect of DAB could be abolished by concomitant incubation with L-alanine and L-methionine, that compete with DAB for the same transport system, while the D-forms of the same amino acids as well as sarcosine had a weak effect. The fibrosarcoma cells were also transplanted s.c. into mice that were subsequently treated with i.p. injections of an isotonic 0.1 M DAB solution. The neoplastic cells were transplanted into totally 90 animals. The mean tumor weight of 42 treated animals was 1.16 g (+/- 0.77 g) compared with the corresponding figures of the 27 untreated mice, that were 2.05 g (+/- 1.22 g), i.e., a 43.4% reduction of tumor growth. There were, however, 17 drug-related deaths. Treatment with DAB generally resulted in weight reduction, at least partly due to loss of appetite, in animals. In addition, neurological symptoms of a specific character could develop among several of the treated animals. The side effects apparently restrict the usefulness of DAB alone as an anti-tumor agent, but since the principle of action of DAB is unique and not shared by other known chemotherapeutics it might offer new possibilities in the combined treatment of neoplastic growth.

Aminobutyrates↗

Biochemical characterization of connective tissue macromolecules derived from cutaneous fibrosarcoma.

Tumor tissue of cutaneous fibrosarcoma was solubilized with salt, acetic acid and salt-extracted after pepsin treatment. Type III collagen was observed in neutral soluble collagen, 1.5 M and 2.4 M NaCl precipitated fractions after pepsin treatment. Type III collagen fraction precipitated with 1.5 M NaCl eluted in the alpha2 region when chromatographed on CM-cellulose without reduction, while the type III collagen partially purified with 1.5 M NaCl eluted between the position of alpha1(I) and beta12 after reduction and alkylation. Analysis of amino acid showed the presence of cysteine and the high content of hydroxyproline following CM-chromatography of 1.5 M NaCl precipitated type III collagen fraction. Acidic glycosaminoglycans were composed of hyaluronic acid, chondroitin sulfate, dermatan sulfate and heparan sulfate, and the first two were major components of fibrosarcoma.

Aged↗

Abnormal 67Ga uptake in a fibrosarcoma of the pericardium with malignant transformation.

A 31-year-old woman presented with general malaise, back pain, and edema of the lower extremities. A chest X-ray film showed an enlarged cardiac shadow and clear lung fields. A pericardial lesion with decreased activity on blood pool imaging and increased uptake on gallium citrate imaging displaced the heart upwards and to the left. The pericardial mass showed an inhomogeneous signal intensity on MRI and was large enough to obstruct the venous return by compressing the heart. At operation, the mass was found to originate from the pericardium and was histologically identified as a malignant fibrosarcoma. Twelve years previously, the patient had undergone an operation for the removal of a pericardial tumor which was histologically identified as a benign hemangioma. In view of the rarity of pericardial tumors, the present tumor is suspected to have undergone a transformation from benign hemangioma to malignant fibrosarcoma.

Adult↗

Repression of stromelysin metalloprotease expression in rat fibrosarcoma cells by dimethylsulfoxide.

Metalloproteases are implicated in conferring invasive properties to tumor cells. We show here that treatment of ras-oncogene-transformed rat fibroblasts with dimethylsulfoxide (DMSO) results in a reversible decrease in stromelysin mRNA. Furthermore, stromelysin expression was found to be repressed by DMSO, but not by glucocorticoid hormone, in a fibrosarcoma cell line showing low AP-1 (fos/jun) transcription factor activity. In two fibrosarcoma cell lines which express high levels of stromelysin and low levels of 68 kDa type IV collagenase, the DMSO-induced decrease in stromelysin expression was paralleled by a decreased invasive propensity.

Animals↗

Detection of multiple tumor suppressor genes for Syrian hamster fibrosarcomas by somatic cell hybridization.

Identification of tumor suppressor gene loci in rodent cell culture systems has relied upon the use of somatic cell hybridization studies. Although normal rodent fibroblasts are capable of suppressing the tumorigenicity of a variety of tumor cells, the lack of complementation in tumor cell x tumor cell hybrids has left the possibility that a single tumor suppressor gene may be responsible for tumor suppression in a particular rodent cell culture system. Using this same approach, we found no evidence for complementation resulting in suppression of the transformed phenotype when three viral oncogene-transformed Syrian hamster embryo (SHE) cell lines and one spontaneously transformed baby hamster kidney (BHK) cell line were fused to benzo[a]pyrene-transformed SHE cells (BP6T-M3). However, v-src oncogene-transformed cell line (srcT) x BP6T-M3 hybrids did demonstrate limited suppression of the transformed phenotype, suggesting at least two complementing tumor suppressor genes in this system. We were able to confirm and extend this finding using another experimental approach with preneoplastic hamster cell lines that are immortal in culture but nontumorigenic in nude mice. We propose that fusion of these preneoplastic cells to various tumor cells may reveal tumor suppressor genes not evident in the tumor cell x tumor cell complementation studies. Subclones of two nontumorigenic, immortal hamster cell lines, 10W and DES4, displayed differing abilities to suppress BP6T-M3 cells in somatic cell hybrids, as quantitated by the ability of the hybrid cells to form colonies in soft agar. With a panel of preneoplastic hamster cell x BP6T-M3 hybrids, a distinct pattern of suppression or expression of the transformed phenotype was observed. Marked differences in this pattern were seen when the same 10W and DES4 subclones were fused to other hamster fibrosarcoma cell lines, indicating different tumor suppressing activities of multiple tumor suppressor genes. Analysis of this data suggests that as few as three or as many as six different tumor suppressor genes may be active in the Syrian hamster embryo cell culture system. Thus, this system may provide a useful model for identifying and studying the effects and regulation of a number of different tumor suppressor genes for fibrosarcomas.

Animals↗

Antitumor effects of a new interleukin-2 slow delivery system on methylcholanthrene-induced fibrosarcoma in mice.

The interleukin-2 (IL-2) mini-pellet, the carrier material of which is a biocompatible and biodegradable atelocollagen refined from bovine skin, contains 1 x 10(6) units of IL-2 and can release IL-2 slowly in vivo by diffusion and dissolution. We have evaluated the antitumor effects of the IL-2 mini-pellet on an established solid murine tumor, methylcholanthrene-induced fibrosarcoma (Meth A). The subcutaneous administration of the IL-2 mini-pellet alone on days 8 and 11 after tumor inoculation significantly inhibited tumor growth. A significant inhibition was also seen when it was combined with the intravenous injection of 5 x 10(7) lymphokine-activated killer (LAK) cells, in comparison to the untreated controls. Moreover, therapy with the IL-2 mini-pellet alone or in combination with LAK cells also prolonged the survival of mice bearing Meth A fibrosarcoma. In order to determine the precise mechanism of action of these antitumor effects, we tested splenocytes of treated mice for cytotoxic activity in vitro and investigated tumor tissues by an immunohistochemical method. On day 2 after the administration of the IL-2 mini-pellet, the lytic activity of splenocytes against both YAC-1 and JTC-11 cells (i.e. NK and LAK activity) was significantly augmented, and on day 7 a massive accumulation of lymphocytes, which were mainly like Thy1+ and/or asialo-GM1+ LAK cells, was seen in the tumor. These findings indicate that the IL-2 mini-pellet is an appropriate system for local administration of IL-2 and can induce LAK-like effector cells at the target site.

Animals↗

A comparison between morphological, rheological and lodgement properties of rat fibrosarcoma cells harvested from solid tumours and cultures.

Vital microscopic studies on tumour cell lodgement in the rat liver have suggested that tumour cells from culture (CTCs) and from solid tumour (STCs) have different rheological properties. In the present study CTCs and STCs from a rat fibrosarcoma were compared in respect to their morphology, rheology and lodgement properties. The ultrastructural examination showed that the CTCs had a larger mean diameter (14.9 microns) than the STCs (11.2 microns). Both cell types had a very irregular nucleus. Surface irregularities provide the CTCs and STCs with a 'membrane excess', i.e. a larger plasmalemma than required to enclose the cells as smooth spheres, amounting to 46.8% and 60.9%, respectively. These values indicate that both CTCs and STCs can be substantially deformed with preservation of the volume and area. The CTCs were stiffer than the STCs when deformed at constant pressure in 6.5 microns glass pipettes, the nucleus appearing to be a significant hindrance to CTC deformation. Five minutes after intraportal injection of radiolabelled CTCs and STCs a much higher percentage of CTCs (82%) than of STCs (20%) remained lodged in the rat liver. The results indicate that the propagation in culture of fibrosarcoma cells alters the morphology and rheology of the cells such that CTCs are not suited for studies in vivo where the spontaneous intravascular dissemination and organ lodgement of tumour cells is simulated.

Animals↗

In vivo activation of NK cells induces inhibition of lung colonization of H-2 positive and H-2 negative fibrosarcoma tumor clones.

The role of different tilorone analogs in the abrogation of the metastatic spread of H-2 positive and H-2 negative tumor clones was studied. Pre-treatment of BALB/c mice with RMI 10,874DA compound completely abolished lung colonization of an H-2 negative (GR9.B9) MCA-induced fibrosarcoma clone in an experimental metastasis assay. This effect was also evident when clones were treated with other tilorone analogs (R11,567DA or R11,513DA). Other H-2 positive and H-2 negative chemically induced fibrosarcoma clones were also tested. The effect was not due to direct toxicity of the tilorone analog on tumor cells, but instead was dependent on NK cells; this was suggested by the finding that treatment of mice with anti-asialo GM1 abrogated the effect of the tilorone analog (RMI 10,874DA compound). Interestingly, the inhibition of lung colonization after intravenous injection was again observed regardless of the H-2 phenotype of the tumor clones, and H-2+ and H-2- clones were similarly inhibited. In vitro assays of NK sensitivity of tumor clones showed that lysis varied depending on the H-2 phenotype of tumor clones, indicating an absence of correlation between in vivo and in vitro results.

Animals↗