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PubMed1981

A model of tumor cell dormancy: effects of anesthesia and surgery.

Three cloned populations of tumor cells obtained from a murine fibrosarcoma were able to remain viable for a long period of time in syngeneic mice which failed to exhibit clinically evident tumors following tumor cell inoculation. Viable tumor cells under such conditions can be considered to be in a dormant state. On the basis of past studies, two of the lines were shown to have low malignant potential, while the third line was shown to have a higher degree of malignant potential. The rates of spontaneous reactivation of tumor growth in animals carrying the low malignant cells were 3 and 4%, while a rate of 30% was observed in animals with the more malignant cells. Treatment of animals carrying the low malignant cells in a dormant state with anesthesia alone, (thiopental) or with anethesia and surgery, increased the rate of reactivation to 20-22%.

Anesthesia↗
PubMed1982

In vitro growth characteristics associated with benign and metastatic variants of tumor cells.

Tumors show a wide range of growth rates in vivo. In general, nonmetastatic (benign) tumors appear to grow slowly, while metastasizing (malignant) tumors proliferate rapidly and contain a large number of dividing cells. In order to analyze if there is a direct relationship between metastatic potential and growth rate (without the influence of host factors), in vitro analyses are necessary. In vitro studies that compared monolayer doubling times and in vivo tumorigenicity rarely demonstrated a correlation between the two parameters. Differences in monolayer growth rates were observed among tumors, but the differences were unrelated to in vivo growth. In contrast, some tumor systems demonstrated a correlation between in vivo growth and/or malignant potential and growth properties observed during anchorage independent growth. Evidence is presented to show that in particular tumor systems, an analysis of colony size and colony morphology during growth in suspension can be used to study the relationship between malignant potential and growth properties.

Animals↗
PubMed1992

Effects of n-3 and n-6 fatty acids on tumor necrosis factor cytotoxicity in WEHI fibrosarcoma cells.

Modulation by fatty acids of the cytotoxic effect of recombinant tumor necrosis factor alpha (TNF) toward WEHI 164 mouse fibrosarcoma cells has been examined. Preincubating the highly TNF-sensitive WEHI clone 13 cells for 44 hr with 50 mumol/L of 20:5n-3, 22:6n-3, 18:3n-6, 20:3n-6 or 20:4n-6 reduced cell survival 22 hr after challenge with TNF (40 ng/L) by 65%, 72%, 60%, 98% and 85%, respectively. In comparison, 18:3n-3, 18:2n-6 and 18:1n-9 had only negligible effects on TNF-induced toxicity. Different extent of fatty acid incorporation into cell total phospholipids or triglycerides could not explain the observed effects on TNF cytotoxicity, and the enhanced cytotoxicity could therefore not be explained merely by an increased unsaturation of the cell membranes. In addition to the fatty acid supplied, preincubation with 18:2n-6, 18:3n-6 or 18:3n-3 also enriched the cells with 20:2n-6, 20:3n-6 and 20:3n-3, respectively, most likely due to chain elongation. The results suggest that the WEHI cells have a low delta 6 desaturase activity, and that n-6 and n-3 acids must have at least 3 or 4 double bonds, respectively, to enhance TNF cytotoxicity in WEHI cells. Dexamethasone partly inhibited TNF-induced cytotoxicity, while cyclooxygenase, thromboxane synthetase or lipoxygenase inhibitors had no or negligible effects. The antioxidant butylated hydroxyanisole (BHA) completely inhibited TNF-induced cytotoxicity, while the structurally and functionally similar antioxidant butylated hydroxytoluene had no such effect, indicating that BHA does not block TNF cytotoxicity through its antioxidant effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

[Surgery of primary malignant bone tumors].

The term primary malignant bone tumors covers a diversity of entities. Tumor resection is preferable in most. In some, surgery alone is sufficient, in others therapy will be based on a combined modality concept. Resection plays the essential role in those tumors treated by surgery alone, e.g., primary osseous fibrosarcoma. The combined modality approach in osteosarcomas or Ewing's tumors provides for additional elements of local therapy (radiotherapy) or systemic treatment (chemotherapy). The relevance of surgery for local control varies in these latter diagnoses. In highly malignant osteosarcoma, where wide margin surgery is of utmost importance, only 10-20% of patients will survive longer than 5 years without aggressive systemic chemotherapy. Radiotherapy in these patients is only indicated when "marginal" or "less than marginal" surgery is expected. In terms of efficacy, radiotherapy is inferior to surgery. In disseminated osteosarcoma, a curative treatment approach will also provide for surgical removal of all metastases. Treatment of primary malignant fibrous histiocytoma (MFH) of bone is identical to osteosarcoma therapy. Since radiotherapy appears to be marginally more effective than in osteosarcoma, both modalities of local therapy are used. Systemic chemotherapy adds an additional benefit for improved survival. Therapy for Ewing's tumor also follows a combined modality approach. The introduction of systemic chemotherapy has raised 5-year survival rates from less than 10% to above 60%. The role of surgery is currently subject to debate. At present, the use of surgery or irradiation for local control is tailored to the individual patient's needs.

Amputation, Surgical↗
PubMed1991

Inhibitory effects of Ixora javanica extract on skin chemical carcinogenesis in mice and its antitumour activity.

Topical application of 100 mg/kg body weight of Ixora javanica flower extract inhibited the growth and delayed the onset of papilloma formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted using croton oil. The extract at the same dose, when administered orally inhibited the growth of subcutaneously injected 20-methylcholanthrene (MCA)-induced soft tissue fibrosarcomas significantly. Oral administration of 200 mg/kg of the extract inhibited the growth of intraperitoneally transplanted sarcoma-180 and Ehrlich ascites carcinoma tumours besides showing an increase in the life span of the treated mice. Toxicity studies showed that the blood urea nitrogen levels were elevated post treatment. The active compounds responsible for the above inhibitory effects on tumour growth were identified as ferulic acid (4-hydroxy-3-methoxy cinnamic acid) and its regionmer 3-hydroxy-4-methoxy cinnamic acid.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Prostaglandin-mediated hypercalcemia in transitional cell carcinoma of the bladder.

A patient with known transitional cell carcinoma of the bladder and hypercalcemia was evaluated for urinary prostaglandin levels when no bone metastases or elevated parathormone levels could be demonstrated. Urinary levels of prostaglandin E metabolite were assessed in relation to serum and urinary calcium levels during treatment. The serum calcium levels decreased from the 13.0 mg. per cent range whenever the rpimary tumor was manipulated (transurethral resection) or when other treatments directed at the tumor were used (radiation therapy and chemotherapy). Serum and urinary calcium levels, and urinary prostaglandin E metabolite decreased when 3 gm. aspirin were given daily. These data suggest that the somewhat unusual hypercalcemia in our patient was caused by a prostaglandin-secreting transitional cell carcinoma. Prostaglandin-secreting tumors are reviewed herein.

Animals↗
PubMed1987

Biologic characterization of human bone tumors IX. Occurrence of macrophages.

Fifty bone tumors were investigated using immunohistological methods for an assessment of the amount and nature of macrophage infiltration. Polyclonal antibodies against lysozyme, alpha 1-antichymotrypsin, and alpha 1-antitrypsin were used as markers, besides certain monoclonal antibodies against blood monocytes and mature tissue macrophages. Particularly high macrophage infiltration was found in malignant fibrous histiocytomas, giant cell-containing osteosarcomas, giant cell tumors of bone, and aneurysmal bone cysts. Moderate infiltrates were seen in some highly malignant osteosarcomas, in fibrosarcoma, and in chondroblastoma. A low macrophage content was observed in some osteosarcomas, in Ewing's sarcomas, chordomas, fibrous dysplasias, aggressive fibromatoses, and cartilage tumors. Osteoclast-like giant cells showed distinctly positive reactions with the monoclonal antibody against mature tissue macrophages. In fibrohistiocytic tumors (MFH, giant cell tumor, non-ossifying fibroma) only macrophages gave positive reactions with those antibodies, whereas the reaction of spindle-shaped tumor cells was always negative. These results strongly indicate that the macrophages found in bone tumors (including those of fibrohistiocytic type) result from reactive infiltration. The autochthonous tumor cells are most probably derived from local mesenchymal cells, and are thus cytogenetically unrelated to the infiltrating macrophages.

Antibodies↗
PubMed1972

Morphology of tumours induced in hamsters by CELO virus, tumour tissue, and tumour cells grown in culture.

Tumours in hamsters, induced by the chicken-embryo-lethal-orphan (CELO) virus, by tumour tissue transplants, or by tumour cells grown in culture, were well circumscribed solid tumours and covered by a thin capsule-like structure. All were fibrosarcomata. However, tumours produced by the 3 inocula exhibited the following histological differences. Neoplasms induced by CELO virus were generally less differentiated and were composed of cells with polygonal or oval nuclei and indistinct cytoplasmic boundaries. Numerous multinucleated bizarre giant cells were found. Those produced by tumour tissue transplants were more differentiated and were composed of spindle shaped cells with abundant collagen fibre formation. Neoplasms induced by tumour cells grown in culture were generally undifferentiated with many mitotic figures and contained numerous giant cells.Cells from tumours induced by CELO virus or tumour transplants produced similar morphologies when cultured in vitro. The cell cultures consisted of large cells with oval or rounded large nuclei and prominent nucleoli. Multinucleated giant cells, cells in mitosis, and a disorganized growth pattern were also characteristic of the cell cultures. However, mitosis and a piling-up of cells occurred more frequently with cell cultures derived from the CELO virus-induced tumour.

Adenoviridae Infections↗
PubMed1977

Relevance of density, size and DNA content of tumour cells to the lung colony assay.

Mouse fibrosarcoma tumours were dissociated and divided into subpopulations of viable cells by centrifugation in linear density gradients of Renografin. Two of these subpopulations, designated Band 2 and Band 4, differed in their clonogenic ability in lung colony assay. The less dense Band 2 cells were significantly more clonogenic than the Band 4 cells (2.9 percent vs 1.4 percent respectively). Each band was further separated on the basis of cell size by centrifugal elutriation. Each size class of cells comprising Band 2 showed higher clonogenic ability than the corresponding size class in Band 4. Thus cell size differences were not responsible for the clonogenic differences between these bands. To determine whether cell-cycle distribution of the tumour cells was responsible for differences in cloning efficiency, flow microfluorometric and premature chromosome condensation methods were utilized. The unseparated and Band 4 populations showed a higher percentage of cells in S and G2 than did the Band 2 populations, but many of the S and G2 tumour cells showed extensive chromosome damage. From this study we conclude that the increased clonogenic ability of the lighter tumour cells is not due to differences in cell size or cell-cycle parameters.

Animals↗
PubMed1982

Syngeneic antitumour antibodies in rats: clearance of cell-bound antibody in vivo and in vitro.

Hooded Lister/Cbi rats bearing the HSN.TC fibrosarcoma produced a high-titre non-complement-binding IgG antibody, and tests in vitro indicated that the syngeneic antibody was specific for this tumour. About 1.4 X 10(5) antibody molecules were bound per cell, a figure one eighth that for cells treated with a high-titre allo-antiserum. When tumour-bearer serum was passively transferred into congenitally athymic rats bearing the HSN.TC tumour the antibody was absorbed out specifically, by comparison with control animals or athymic rats bearing an unrelated tumour that was also syngeneic in Hooded rats. The kinetics of loss of antibody from the surface of HSN.TC cells has been monitored in vitro and the antibody has been found to have an extended half-life at the cell surface (greater than 40 h).

Animals↗