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[Study on a tumor associated antigen on a rat fibrosarcoma cell line--chemical structure of an antigen reactive to a rat natural antibody].

Conventionally bred rats possess a natural antibody (NA) in their sera, which is cytotoxic in its effect on a KMT-17 tumor cell line derived from a fibrosarcoma induced by 3-methylcholanthrene and can be absorbed by normal rat tissues. We have succeeded in isolating and purifying an antigen reactive to NA from the tumor cells as a glycosphingolipid (GSL). GSLs from the tumor cells were separated into neutral and acidic fractions. The former fraction was judged to be antigenic as detected by its capacity to absorb NA. The antigenic fraction was further separated into 7 fractions, Fr.A to Fr.G, by silicic acid chromatography. The antigenic activity was detected in only Frs.D and E, although Fr.D was a more potent antigen than Fr.E. Chemical and immunochemical analyses showed that both the fractions are lactoneotetraosylceramide (paragloboside), Gal (beta 1-4) GlcNAc (beta 1-3) Gal (beta 1-4) Glc (beta 1-1) ceramide, and that the more active GSL, Fr.D, contains larger amounts of long fatty acid chains. Inhibition studies using disaccharides and monosaccharides indicated that a N-acetyllactosamine moiety, Gal (beta 1-4) GlcNAc, is a specific site of the GSL antigen to NA. These results suggest that a sugar chain portion of this GSL is required for defining specificity and that the ceramide portion plays a role in potentiating the antigenicity of this GSL antigen.

Animals↗

3H-arginine-rich cationic proteins in cytosol of fibrosarcoma, induced by methylcholanthrene in rats.

With the use of 3H-arginine it is shown that among soluble cytosol of fibrosarcoma, induced by 20-methylcholanthrene in rats there appear cationic proteins rich in arginine with content of amino acid of about 10%. The amount of these proteins in cytosol fraction is higher than in cytosol of another types of experimental tumors. The role of arginine-rich cationic proteins in cytosol fraction is briefly discussed.

Animals↗

Distribution of 64copper in the blood and different tissues of mice bearing induced fibrosarcoma.

To understand the nature of copper distribution during malignancy, 27 strains A/RB mice with fibrosarcoma were used. Tracer methodology with radioactive isotope of copper (64Cu) was applied. In the study made at different time intervals after isotope administration whole blood plasma and different tissues like liver, heart, spleen kidney and brain were investigated. Liver nuclear fractions were also examined. Distribution of 64Cu in different tissues reflected interesting results. While the incorporation pattern in the liver showed gradual fall from 8 h of isotope administration, the tumor tissue exhibited gradual elevation, compared to the controls. The effect of this finding is discussed.

Absorption↗

[Dermatofibrosarcoma protuberans: transition to fibrosarcoma].

We report on two patients suffering from dermatofibrosarcoma protuberans showing areas of fascicular fibrosarcoma. Whereas the mitotic rate was very low in the classic storiform parts of the tumor, the dedifferentiated areas presented an increased mitotic rate up to 10 to 15 mitoses/10 HPF. Metastases did not occur. Clinically, such a tumor may be treated like typical dermatofibrosarcoma protuberans as long as the sarcomatous component is small and not prevalent.

Back↗

[Subcutaneous fibrosarcoma in a lion (Panthera leo)].

A subcutaneous growth developed on the left side of a zoo lion. The growth enlarged over a period of 3 months. A diagnosis of fibrosarcoma was made on account of the history, clinical and histological examinations. The lion was killed 3 weeks after surgical removal of the tumour. The autopsy showed no evidence of metastases. A foreign body (wire) was discovered in the abdominal cavity but no association was found between the lesion caused by the wire and the malignancy.

Animals↗

[Congenital fibrosarcoma. Apropos of 2 cases].

Two cases of congenital fibrosarcoma are presented. Both tumors showed histological features of malignancy, but were successful treated with simple resections. Recurrent tumor does not seem to predispose to metastatic disease. Local excision is the initial treatment of choice for lesions occurring in newborns and infants.

Abdominal Neoplasms↗

Association of macrophage activation with antitumor effect on rat syngeneic fibrosarcoma by Nocardia rubra cell wall skeleton.

The antitumor activities of the cell wall skeleton (CWS) of Nocardia rubra were demonstrated for syngeneic fibrosarcoma (AMC-60) in ACI/N rats in regard to macrophage activation. In the 24-hr cytolytic test, activated macrophages which were fractionated from peritoneal exudate cells induced by i.p. injection of Nocardia CWS showed significant cytolytic activity for [125I]iododeoxyuridine-labeled tumor cells. Activated macrophages also strongly inhibited [3H]thymidine incorporation into the tumor cells during the 24-hr cytostatic test. When tumor cells were inoculated s.c. with activated macrophages in the Winn-type transfer assay, subsequent tumor growth was significantly inhibited. Repeated i.p. injection of the CWS seemed to enhance these antitumor activities of macrophages. The therapeutic effect of Nocardia CWS was assessed with the ascites tumor and with the solid tumor inoculated i.m. into the hind leg. In the former treatment, repeated i.p. injections completely prevented the accumulation of ascites fluid and resulted in prolongation of the survival period. The peritoneal macrophages harvested from these survivors had a strong cytolytic activity for tumor cells in the cytolytic test. In the latter treatment, repeated intratumoral injections inhibited the growth of primary tumor and prevented metastasis. Furthermore, peritoneal resident macrophages from these tumor-bearing rats treated intratumorally with the CWS were found to be cytolytic for tumor cells in the cytolytic test.

Animals↗

Properties of metastatic and nonmetastatic cloned subpopulations of an ultraviolet-light-induced murine fibrosarcoma of recent origin.

The present studies were designed to evaluate whether tumor cell properties such as growth rate, chromosome number, anchorage-independent growth, susceptibility to lymphocyte- or macrophage-mediated lysis in vitro, and antigenicity in vivo correlated with metastatic potential. A murine fibrosarcoma of recent origin induced in a C3H- mouse by chronic irradiation with ultraviolet light was used. Cells from the parent tumor and its clones were grown in culture. No single property of tumor cells that was measured in vitro or in vivo predicted or correlated with their metastatic potential. In order for metastasis to occur, all steps of the process must be completed. Therefore, interruption of the sequence at any stage can prevent the production of visible metastasis. It was concluded that the search for a single property common to all metastatic cells in a large variety of neoplasms is likely to be unproductive.

Animals↗

Analysis of immunosuppressor cells induced by immunization of solubilized tumor-associated antigens prepared from a rat fibrosarcoma.

Soluble tumor antigens were prepared from chemically-induced rat fibrosarcoma KMT-17 cells by sodium deoxycholate (DOC) extraction. Significant responses detected by the footpad assay and Winn assay were demonstrated in rats immunized with DOC extract. However, rats previously immunized with DOC extract showed a significant enhancement of tumor growth when challenged with KMT-17 cells. This enhancement was specific for the tumor line used. The tumor-neutralizing ability of KMT-17 immune spleen cells was abrogated when DOC extract immune spleen cells were added to a mixture of KMT-17 cells and KMT-17 immune spleen cells. This suppressive activity of the spleen cells was diminished by the treatment with anti T serum and complement. After fractionation of DOC extract immune spleen cells by the Ficoll density gradient, the cells in the light layer showed an enhancing effect on tumor growth, whereas the cells in the heavier region of the gradient had an inhibiting effect. These results suggested that both immunosuppressor cells and cytotoxic cells were induced in rats immunized with DOC extract.

Animals↗

Characterization of high- and low-metastatic clones derived from a methylcholanthrene-induced murine fibrosarcoma.

A methylcholanthrene-induced fibrosarcoma (3AM) and several of its clones were evaluated for pulmonary metastasis, growth rate, and chromosome composition. Heterogeneity was observed in the three parameters, and no correlation was found between growth rate and metastatic potential. Furthermore, three clones (10, 34, and 27) were identified with distinctive, high or low, metastatic potential and marker chromosomes. The marker chromosomes characteristic for each clone were identified in the early passages of the parental 3AM line, indicating the preexistence of the different cell types in the original neoplasm. The three clones were then characterized as to tendency to adhere to vascular endothelium, immunogenicity, and antigenic specificity. Clone 10, with two large metacentric markers (T2, 4 and T10, 15) and the highest metastatic potential (221 foci/lung), expressed the highest endothelial attachment and immunogenicity. Clone 27 was characterized with an extremely low rate of metastasis (nine foci/lung) and a T2, 7 large acrocentric marker, while clone 34 was characterized with a moderate rate of metastasis (107.5 foci/lung) and a T4, 16 acrocentric marker. Antigenically, clone 10 cross-reacted with clones 34 and 27 and 3AM, while clones 27 and 34 cross-reacted with clone 10 and 3AM but not with each other, suggesting that, within the original tumor, there were common tumor antigens shared by some cells but no universal antigen shared by all cells.

Animals↗

Soluble factors produced during an immune response regulate Ia antigen expression by murine adenocarcinoma and fibrosarcoma cells.

LT-85 is an alveologenic adenocarcinoma of C3Hf/HeN mice. Comparisons of the in vitro and in vivo surface properties of these cells revealed that under normal conditions, they expressed I-A and I-E antigens iv vivo only. By using clonally derived cells, it was established that this phenomenon was not due to the selection of an Ia antigen-positive tumor cell subpopulation, but resulted from phenotypic conversion of Ia antigen-negative tumor cells. These tumor cells and 1053 cells (a fibrosarcoma of C3H/HeN MTV- mice) could, however, be induced to express I-A, I-E, and much higher levels of H-2 antigens in vitro by co-culturing them with spleen cells from LT-85 tumor-bearing C3H/HeN MTV- mice. In vitro induction of Ia and H-2 antigens did not result from contaminating splenocytes or from antigen transfer, because splenocytes from BALB/c (H-2d) mice immunized with A/J (H-2k/d) cells were able to induce the expression of Iak antigens by both tumor cell lines. It was found that this phenomenon was neither H-2-restricted nor antigen-specific. The results clearly indicated, however, that an immune response was required to generate phenotypic conversion of the tumor cells, both in vivo and in vitro. It was further found that soluble, rather than cellular, factors produced during an immune response induced the expression of Ia antigens by LT-85 and 1053 tumor cells. In contrast to what has been reported about the induction of Ia antigens on macrophages and normal epithelial and endothelial cells, the induction of Ia antigens on LT-85 and 1053 cells did not appear to require T cells, and did not involve gamma-interferon. These findings demonstrate that some tumor cells are capable of altering their MHC antigen phenotype in response to factors produced during an immune response in vivo or in vitro. Because of the involvement of Ia antigens in several aspects of immune phenomena, the ability of tumor cells to differentially express Ia antigens in response to environmental factors may have profound effects on host-tumor interactions. Furthermore, the differences seen in the phenotypes of tumor cells grown in vitro and in vivo suggest that in vitro methodologies of tumor cell characterization may not present a complete picture of the natural state of the tumor cell surface.

Adenocarcinoma↗

Immunomodulating activities associated with the cytosol fraction of a 3-methylcholanthrene-induced rat fibrosarcoma.

Cytosol fraction(s) from McFiFi2(s) fibrosarcoma cells (Fcc), isolated from either cultured cells or solid tumors induced in F344 rats, produced a dose-related inhibition of lymphoproliferative responses to several mitogens, whatever the lymphoid organ or the animal species used as the source of lymphocytes. Only stimulated human lymphocytes were not Fcc inhibited; instead, Fcc was a potent stimulator of their spontaneous proliferation. Fcc cytostatic activity was not effective in various cycling cell lines and was restricted to mitogen-stimulated lymphocytes. Fcc, a primary tumor product, did not induce suppressive cells and was unable to prevent mitogen cell surface binding. However, expression of its modulating effect was accelerated by the simultaneous presence of the mitogen. Moreover, Fcc produced its suppression by interrupting lymphocyte activation at some point within the G0-G1-phase transition. Molecular sieving showed that Fcc contains at least two factors with suppressive (mol wt, approximately 3,000) and stimulatory (mol wt, greater than 5,000) activities, respectively.

Adjuvants, Immunologic↗

[Antitumor activity of schizophyllan (SPG) against syngeneic ACI/N rat tumor, AMC-60 fibrosarcoma and BC-47 bladder cancer].

The antitumor activity of schizophyllan (SPG) against syngeneic ACI/N rat tumor, AMC-60 fibrosarcoma and BC-47 bladder cancer was investigated. Intramuscular injection of SPG caused a marked suppression of AMC-60 tumor growth. Results obtained with cytotoxicity tests in vitro and lymphoblastogeneic response in vitro suggest the association of enhanced macrophage cytostasis and high reactivity of lymphoid cells with the resistance of the host to AMC-60 tumor. Moreover, SPG showed pronounced antitumor activity against BC-47 bladder cancer. The highest therapeutic effectiveness was obtained when SPG injection was started at an advanced stage of the tumor, 4 out of 15 rats treated being completely cured of cancer. Cytotoxicity tests in vitro and neutralization tests in vivo indicated the important role of cytotoxic lymphocytes as well as activated macrophages in the host defence mechanism against BC-47 cancer. This, taken together with the fact that the rats cured completely by SPG therapy acquired transplantation resistance to BC-47 cancer, shows that SPG may promote tumor immunity in the host.

Animals↗

Fibrosarcoma of the breast.

A total of 5 583 symptomatic patients were referred for xeromammography at the Mammographic Clinic, Johannesburg General Hospital, between June 1974 and January 1979. Four hundred and fifty-eight carcinomas and 3 sarcomas were recorded. The incidence of carcinoma in our series was 7,9% and that of sarcoma 0,65%, while there was a 0,21% incidence of pure fibrosarcoma. Comparison is made with world literature.

Adenocarcinoma, Mucinous↗

Studies of the immune response against a polyoma virus-induced fibrosarcoma in BALB mice using the Winn's tumor neutralization assay.

Rejection of a polyoma-virus induced fibrosarcoma was studied by the adoptive tumor neutralization assay. This assay showed that polyoma immune spleen cells had a specific growth inhibiting effect on admixed polyoma tumor cells; they only delayed the tumor growth of an irrelevant cell line. We provide evidence both for the role of T-cells in this rejection and for a possible participation of macrophages. T-cells action was not strictly H-2 restricted but H-2 preference was observed. Adoptive protection of nude mice showed that T-cells of the recipient did not participate in the reaction.

Animals↗

The life span and osmotic fragility of erythrocytes in mice bearing benzo(a) pyrene - induced fibrosarcoma.

Red cell survival studies in mice with benzo(a) pyrene [B(a)p]-induced fibrosarcoma indicate marked reduction in RBC 51Cr t1/2. In contrast, the t1/2 of erythrocytes from B(a)p injected but tumor-free mice was not declined. Increasing tumor burden resulted in increment in the severity of this disorder, and preincubation of normal red cells with tumor supernatant caused significant reduction (p less than 0.05) in 51Cr t1/2. It is suggested that the observed alteration in RBC life span may be due to the effect of tumor. Apparently, both intrinsic and extrinsic cellular defects could be implicated for this abnormality. However, the shortened survival cannot be attributed to altered osmotic fragility, since the erythrocytes of the fibrosarcomatous mice were more resistant to hypotonic hemolysis in vitro.

Animals↗