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K M Tveit

Publications and source records attributed to K M Tveit.

71 records · Page 4Linked to original sources
PubMed1984

Multicellular spheroids grown directly from human tumour material.

Human tumour cells from surgical material were grown as multicellular spheroids. In 16 out of 20 cultures spheroids with a diameter of more than 250 microns could be observed. In 6 out of 20 cultures more than 30 spheroids with a diameter of at least 300 microns were obtained, i.e. 30% of the cultures fulfilled the criterion for a possible chemosensitivity test on primary cell spheroids. A study of stained sections from the spheroids and the respective tumours, showed that the morphology of the spheroid was very similar that of the tumour from which the cells were derived. Samples from 9 malignant melanomas, 4 bladder carcinomas, 2 renal-cell carcinomas, 2 ovarian carcinomas, 1 lymphoma, 1 colon carcinoma, and 1 schwannoma were tested for spheroid growth. Spheroids were obtained from at least one representative of all these tumour types. However, investigations involving larger numbers of tumours are needed to find out which tumour types are most suitable for further biological characterization of primary cell spheroids and tests for therapy response.

Adult↗
PubMed1983

Stability of cadmium resistance and metallothionein levels in vitro and in vivo.

Cultured cells can be adapted to large concentrations of the toxic cadmium ion, apparently by induction of synthesis of the Cd-binding protein metallothionein (MT). One human epithelial line derived from normal skin (HE100) and one murine fibroblast line, derived from L cells (C1 1D100), were used to study the stability of Cd resistance, the MT levels following omission of Cd, and the inducibility of MT synthesis in cells on reexposure to Cd. In the murine cells there was no significant loss of resistance during a 4-week period either after cultivation in vitro or after growing the cells in nude mice. In the human cells a decrease (50%) in resistance was noted the first week after Cd omission. After removing Cd from the cells, a rapid decrease in MT content was demonstrated. After 3 weeks of cultivation only trace amounts were left in both cell lines. However, approximately 60% (HE100) and 80% (C1 1D100) of the previous levels were demonstrated after reexposure to maximum tolerable doses for 24 hr. The data indicate that the degree of stability of Cd resistance is dependent on the capacity in cells for an immediate de novo synthesis of large amounts of MT on reexposure to Cd. The animal experiments demonstrate that Cd resistance is maintained even after growing the cells in vivo.

Animals↗
PubMed1982

Colony growth and chemosensitivity in vitro of human melanoma biopsies. Relationship to clinical parameters.

To study the usefulness of an in vitro colony-forming assay in predicting individual clinical responses to chemotherapy, tumor cells obtained from 150 melanoma metastases (119 patients) were grown in soft agar according to the method of Courtenay and Mills (1978), and tested for sensitivity to DTIC, CCNU, vinblastine, procarbazine, abrin and ricin. In 83% of the cases colony formation was observed (plating efficiency, PE, greater than 0.01%). Twenty-seven per cent of the tumors gave PEs greater than 1%, 45% gave PEs in the range 0.1-0.9%, whereas 11% of the tumors gave 0.01-0.09%. The PEs were not correlated with the degree of pigmentation or with the clinical course. Evaluable chemosensitivity data were obtained on 104 metastases from 83 patients. Large differences in sensitivity were seen. In cases which were evaluable both in vivo and in vitro a clear correlation was found between the in vitro chemosensitivity, expressed as the expected growth delay, and the clinical response to chemotherapy. Tumors from patients with partial response, mixed response or stable disease after prior progression, all had rather high in vitro sensitivity to the drug used (expected growth delay greater than 2.0), whereas patients with progression had lower sensitivity. The results confirm that the soft agar method used here provides good culture conditions for human melanoma cells and show that chemosensitivity data can be obtained in a high percentage of melanoma patients. The approach used seems promising in aiding clinicians to adjust chemotherapy to individual patients.

Antineoplastic Agents↗
PubMed1981

The usefulness of human tumor cell lines in the study of chemosensitivity. A study of malignant melanomas.

The chemosensitivity of human melanoma cells has been studied before and after continuous in vitro culture. Altogether, nine cell lines were studied, two derived from patients' biopsies, and seven from xenografts in athymic mice. The sensitivity to the agents DTIC (Dacarbazine), CCNU (Lomustine), procarbazine, vinblastine, abrin and ricin was assayed. Furthermore, in five cases the chemosensitivity of the cell lines was compared to that of tumors obtained by injecting the cell lines into athymic mice. In all cases the sensitivity was measured in an in vitro soft agar assay. Upon cultivation in vitro, two of the cell lines, one derived from a patient's metastasis and one from a xenograft in athymic mice, showed marked increases in sensitivity to some of the drugs, whereas sensitivity to other drugs showed little or no change. For the other cell lines small, but definite increases or decreases in chemosensitivity were observed. Permanent cultures showed the same chemosensitivity as early subcultures. The tumors formed by injecting the cell lines into athymic mice showed moderate changes in chemosensitivity, as compared to the cell lines in vitro. The data indicate that considerable changes in chemosensitivity may occur when cells are brought from in vitro to in vitro conditions and vice versa and that such changes may be highly specific. Therefore, although cell lines may be useful in some respects, they should be used with caution in attempts to evaluate quantitatively the sensitivity of human tumors to cancerostatic drugs.

Animals↗
PubMed1981

Cultivation of human melanomas in soft agar. Factors influencing plating efficiency and chemosensitivity.

As part of a programme to study the predictive clinical value of a soft agar assay for measuring chemosensitivity of human melanomas in vitro, we have observed the effect of three disaggregation methods on the yield of tumor cells, plating efficiency in soft agar and chemosensitivity. The yields and plating efficiencies obtained, as well as sensitivity to DTIC, CCNU, vinblastine and abrin, were about the same whether collagenase/pronase/DNase-treatment, trypsin/EDTA-treatment or mechanical treatment was used. When melanoma xenografts of different sizes were studied, an inverse relationship between tumor size and plating efficiency was found, whereas chemosensitivity was unaffected by tumor size. The highest plating efficiencies of melanoma cells, both from patient biopsies and from xenografts, were obtained when red blood cells were present and a low oxygen concentration (5%) was used. The results demonstrate that, in the case of melanomas, the fraction of tumor cells that are clonogenic in vitro depends on the size of the tumors, and even more so on the culture conditions used. An important finding was that chemosensitivity in vitro appears to be unaffected by the disaggregation method and by tumor size.

Abrin↗
PubMed1981

Comparison of two soft-agar methods for assaying chemosensitivity of human tumours in vitro: malignant melanomas.

Two soft-agar methods for assaying chemosensitivity of human cancers in vitro were compared with respect to colony morphology, plating efficiency (PE) and chemosensitivity of human melanomas. In 9 xenografts and 9 patients' biopsy specimens Method A (essentially that of Courtenay & Mills, 1978) gave considerably higher PE that Method B (essentially that of Hamburger & Salmon, 1977) and, in contrast to Method B, the number of colonies was proportional to the number of cells plated. Evidence was obtained that the observed differences in PE could be attributed to the low O2 concentration and the presence of rat red blood cells in Method A. Colony morphology was similar in the 2 assays. When cells from 4 xenografted melanomas were treated in vitro with DTIC, CCNU, vinblastine and abrin, and the inhibition of colony formation was assayed concurrently in the 2 soft-agar methods, the tumour cells appeared to be more sensitive to 3 of the drugs in Method B than in A. The results demonstrate that chemosensitivity data obtained with the 2 assays cannot be directly compared.

Abrin↗
PubMed1981

Do cell lines in vitro reflect the properties of the tumours of origin? A study of lines derived from human melanoma xenografts.

The characteristics of 7 human melanoma cell lines were compared with those of the xenografts from which they were established. The ultrastructure, melanin content, isozyme pattern and chromosome numbers of the cell lines were closely similar to those of the corresponding xenografts. The different cell lines gave rise to colonies in soft agar of size and morphology similar to the parent xenografts, and the plating efficiencies were clearly correlated. However, no correlation was found between the growth rates in vivo and either the doubling times and saturation densities in monolayer cultures or the plating efficiencies in soft agar. Moreover, one of the cell lines lost its tumorigenic ability upon establishment in culture. Thus, although the properties of the cell lines by and large reflected those of the parent xenografts, important inconsistencies were seen. The data emphasize that extrapolations from continuous cell lines in vitro to tumour cells in vivo are not necessarily valid. A high content of cellular fibronectin was correlated with a compact colony morphology in soft agar and rapid attachment and spreading on plastic. The growth rates and cellular morphology of the cell lines were strongly influenced by TPA, DMSO, retinoic acid and theophylline, but not by alpha-melanocyte-stimulating hormone. A murine cell line established from one of the xenografts grew in soft agar and produced sarcoma in mice. The malignant murine cells had arisen by transformation of murine stromal cells during the first subcultures in vitro, possibly caused by a factor produced by the human melanoma cells.

Animals↗
PubMed1980

In vitro sensitivity of human melanoma xenografts to cytotoxic drugs. Correlation with in vivo chemosensitivity.

Single-cell suspensions prepared from five human melanomas, grown serially as xenografts in athymic nude mice, were exposed in vitro to increasing concentrations of DTIC (Dacarbazine), CCNU (Lomustine), procarbazine, vinblastine, and the cancerostatic lectins abrin and ricin. The in vitro chemosensitivity of the cells, as measured by the drug concentrations required to inhibit colony formation in soft agar by 50%, was correlated with the growth delay of the xenografts in vivo, previously observed after treatment of the animals with maximum tolerable doses of the same drugs. It was found that for each drug the in vitro sensitivity of the different xenografts was strongly correlated with their response in vivo. The results provide evidence that the soft agar test, as carried out here, adequately reflects the relative sensitivity of the xenografts in vivo. The data indicate that human xenografts may be used to develop quantitative in vitro chemosensitivity tests.

Abrin↗
PubMed1980

A human melanoma cell line established from xenograft in athymic mice.

A human melanoma cell line with unusually high growth potential was established from a xenograft growing in athymic mice. When xenograft fragments were cultured in vitro, melanoma cells grew out rapidly without any contamination of mouse stromal cells. An established cell line, FME, derived from this tumour, grew both in monolayer and in shaker suspension culture with doubling times of about 20 h. The cells grew easily at low serum concentrations and could even be cultured in serum-free medium supplemented with insulin and transferrin. The cultured cells were hyperdiploid, as were the cells of the xenograft. The cells grew easily in soft agar and formed tumours in athymic mice. When growing exponentially, the cells were almost unpigmented, but when grown to high density, their melanin content increased. Upon treatment with dimethyl sulphoxide (DMSO), retinoic acid and theophylline, as well as with the tumour promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), the cells showed growth inhibition and increased melanin synthesis.

Animals↗
PubMed1980

Human embryonal carcinoma grown in athymic mice and in vitro.

Tissue from 19 human testis tumors was transplanted into athymic mice. One embryonal carcinoma, ECCS, grew rapidly, and this tumor was studied both as a xenograft and an in vitro culture of xenograft-derived tumor cells. Xenografts showed no evidence of differentiation. The embryonal carcinoma cells were heteroploid and showed alkaline phosphatase activity. When tumor cells from the xenografts were grown in vitro, the cells formed aggregates resembling embryoid bodies with epithelium-like cells in the periphery. Regularly, another population of mouse cells which showed several criteria of malignancy overgrew the culture and could be subcultured continuously. These abnormal cells may result from an in vivo or in vitro transformation of mouse stromal cells.

Alkaline Phosphatase↗
PubMedDate not supplied

Colony formation in urinary bladder carcinoma. Relationship to DNA flow cytometry, stage and histopathology.

Tumour cells from 74 biopsies from human urinary bladder carcinomas were cultivated in a semisolid system (Courtenay and Mills method). In 51 cases DNA flow cytometry (FCM) was performed. Significant growth was obtained in 53 of 74 cases (71.6%), and good quality DNA histograms from FCM were obtained in all 51 attempts. No correlations between clinical or histopathological data and plating efficiency (PE) were found, nor between ploidy and PE. However, a very high S-phase (greater than 15%) correlated with a low PE. This work shows that bladder carcinoma cells can be studied in a semisolid agar system. It also suggests that there exists no correlation between PE and DNA FCM data or clinical or histopathological data.

Biopsy↗
PubMedDate not supplied

Colony-forming ability of human ovarian carcinomas in the Courtenay soft agar assay.

One hundred and twenty-one ovarian carcinomas were cultivated in soft agar according to the Courtenay & Mills (C-M) soft agar method. 71% of the tumours formed colonies, and 54% formed more than 30 colonies. Tumour cells from malignant fluids grew more frequently than did solid tumours, whereas the plating efficiencies (PEs) were higher in the case of solid tumours. In general, the PEs were higher and more tumours formed colonies in the C-M method compared to the Hamburger-Salmon (H-S) method. The colony-forming ability did not show statistically significant correlation to histopathological type and grade, previous treatment and S-phase fraction, but was related to DNA ploidy. In poorly differentiated tumours a high colony-forming ability was associated with a poor prognosis, whereas the opposite was found in well and moderately differentiated tumours. Differential dose-response relationships were obtained after in vitro treatment with anticancer agents.

Agar↗