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Biomedical subjects

E Helseth

Publications and source records attributed to E Helseth.

48 records · Page 3Linked to original sources
PubMed1989

Effects of interferon-gamma and tumor necrosis factor-alpha on clonogenic growth of cell lines and primary cultures from human gliomas and brain metastases.

In this study we tested the effect of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and a combination of these immunotherapeutics on clonogenic growth of cell lines and primary cultures of malignant human brain tumors. Out of 29 primary cultures studied, 5 were inhibited 50% or more by IFN-gamma (10 ng/ml), 6 were inhibited 50% or more by TNF-alpha (10 ng/ml) and 14 were inhibited 50% or more by a combination of IFN-gamma (10 ng/ml) and TNF-alpha (10 ng/ml). The doses of the immunotherapeutics used in this in vitro study are achievable in serum after intravenous administration of IFN-gamma and TNF-alpha without causing unacceptable side effects. We believe that some glioma patients and some patients with brain metastases will benefit from receiving treatment with IFN-gamma, TNF-alpha or a combination of these immunotherapeutics. The patients should be selected for treatment with these immunotherapeutics according to in vitro sensitivity results.

Cell Division↗
PubMed1988

The effect of type beta transforming growth factor on proliferation of clonogenic cells from human gliomas.

Type beta transforming growth factor (B-TGF) is a potent regulator of cell growth and differentiation. Growth of many human tumour cell lines are inhibited by B-TGF. The effect of B-TGF on proliferation of clonogenic cells from 12 human glioma biopsies was registrated in a thymidine incorporation assay. B-TGF appeared to be a potent growth inhibitor for some gliomas, while it had no effect on others. Maximum inhibition was about 60%. Though not significant, glioblastomas appeared to be less sensitive to inhibition by B-TGF than astrocytomas and oligodendrogliomas. Very little is known about the growth inhibitory action of B-TGF. The negative autocrine growth theory for cancer cells postulates that a reduced production, or production of a defective growth inhibitor normally found in the cell, may account for the autonomous nature of some cancer cells. In view of this theory, we searched for B-TGF in protein extracts from a glioblastoma cell line, T-MGl, whose growth was inhibited by B-TGF. Protein extract from T-MGl cells was analysed for B-TGF activity using a soft agar colony formation assay with normal rat kidney fibroblasts. B-TGF was not found in the extract. Since, according to the literature B-TGF has been found in all other cell lines examined, we believe that there may be a lack of B-TGF or an altered B-TGF in the gliomas whose growth are inhibited by B-TGF. This problem will be studied further.

Brain Neoplasms↗
PubMed1988

The effects of type beta transforming growth factor on proliferation and epidermal growth factor receptor expression in a human glioblastoma cell line.

Type beta transforming growth factor (B-TGF) is a potent growth inhibitor to many human tumor cell lines. Very little is known about the mechanism for this growth inhibitory action of B-TGF. We here report the effect of B-TGF on proliferation and epidermal growth factor receptor (R-EGF) expression in a human glioblastoma cell line named T-MG1. B-TGF inhibit the soft agar growth of T-MG1 cells. Maximum inhibition was 70%, achieved with 0.5 units B-TGF. B-TGF had no effect on monolayer growth of T-MG1 cells. T-MG1 cells contained abundant R-EGF, which could be divided into two subpopulations, one high affinity and one low affinity population of R-EGF. Treatment with B-TGF caused an initial decrease (0-6 h) in EGF-binding, followed by an increase in EGF-binding which reached maximum after 24 h exposure to B-TGF. Since addition of EGF to agar cultures gave no additional increase in inhibition by B-TGF and EGF alone had no inhibitory effect, we believe that binding of EGF to its receptor is not part of the pathway mediating the inhibitory effect of B-TGF. All neoplastic cells have lost some measure of growth control and the cellular elements involved are growth factors, growth factor receptors and oncogenes. T-MG1 cells contain abundant R-EGF and this may partly explain their malignant nature (malignant nature is here defined as ability to proliferate in agarose). Type alpha transforming growth factors, which in some cancer cells act as uncontrolled autocrine growth factors, were not found in protein extracts from T-MG1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Type beta transforming growth factor and epidermal growth factor suppress the plasminogen activator activity in a human glioblastoma cell line.

In the human glioblastoma cell line, T-MG1, plasminogen activator activity (PA-activity) was demonstrated by using the chromogenic substrate S-2251. Using monoclonal antibodies against human urokinase type PA (u-PA) and human tissue type PA (t-PA), only u-PA activity was found in T-MG1 cell extracts. The u-PA activity in T-MG1 cells was suppressed in a dose-dependent manner by B-TGF and EGF after 24 hours of exposure to these growth factors. Twenty units of B-TGF caused a decrease in PA-activity of 80%, while 10 ng/ml EGF gave a decrease in PA-activity of 60%. The suppressive effects of B-TGF and EGF were observed after 2 hours and 4 hours of incubation, respectively and sustained for at least 24 hours. The effects of B-TGF and EGF were not antienzymatic, but rather mediated through regulatory mechanisms. In view of the capacity of invasive growth of gliomas and the potential role of PA in invasive growth, the suppression of PA-activity in gliomas by B-TGF and EGF may be of importance.

Aged↗
PubMed1988

Effects of type beta transforming growth factor in combination with retinoic acid or tumor necrosis factor on proliferation of a human glioblastoma cell line and clonogenic cells from freshly resected human brain tumors.

Type beta transforming growth factor (beta-TGF) is a potent regulator of cell growth and differentiation. The human glioblastoma cell line, T-MGI, was growth inhibited by beta-TGF under anchorage independent conditions. The antiproliferative effect of beta-TGF was potentiated to nearly total arrest by low doses of retinoic acid (RA) or tumor necrosis factor (TNF), while epidermal growth factor, platelet-derived growth factor, interleukin-2, and gamma interferon did not have this potentiating effect. The potentiation of the beta-TGF effect by RA and TNF could not be explained by modulation of the epidermal growth factor receptor, the beta-TGF receptor, or the TNF receptor. beta-TGF alone and in combination with RA or TNF were further tested on primary cultures from freshly resected human glioma biopsies (n = 13). There was great individual variation in sensitivity to beta-TGF, RA, or TNF. The astrocytoma and oligodendroglioma cells were inhibited to various degrees by beta-TGF or TNF, while most of the glioblastomas were not sensitive to these agents. Most of the biopsies were stimulated by RA. RA or TNF did not potentiate the growth inhibitory effect of beta-TGF on biopsy cells. We therefore think it unlikely that beta-TGF in combination with RA or TNF will be effective agents in the treatment of gliomas.

Adjuvants, Immunologic↗
PubMed1988

An isotope agarose assay for rapid testing of the sensitivity of glioma biopsies to chemotherapeutic drugs and biological response modifiers. Effects of BCNU, vincristine, lymphokines and the recombinant agents interferon alpha 2c, interferon gamma and tumour necrosis factor.

A method based on growth of cells from glioma biopsies in a triple layer agarose system has been used to test the sensitivity of the tumour cells to different chemotherapeutic and immunotherapeutic agents. A special agarose that could be melted at 65 degrees C, enabled registration of proliferation by an easy and precise thymidine incorporation technique. The well known concept that agarose permits proliferation of malignant cells and inhibits growth of benign cells was confirmed in this assay by using the malignant glioma cell lines T-MG 1 and U 251 MG, and the benign glia cells T-BG 2 and T-BG 3. All of the 15 glioma biopsies grew exponentially during the first 7 days. The correlation between thymidine incorporation on day 7 and colony number on day 14 was very good for the glioma cell line (r = 0.96) and also for the glioma biopsies (r = 0.89), indicating that the sensitivity evaluation can be done as early as 7 days after the operation. Lymphokines, made by BCG-stimulated lymphocytes, had a strong inhibitory effect on the growth of some glioma biopsies, while others were only slightly inhibited or even stimulated. There was also a huge variation in the sensitivity of the biopsies to BCNU, but the sensitivity pattern was completely different for BCNU and lymphokines. rIF-A had a moderate inhibitory effect on growth of the biopsies, while rTNF had a weak inhibitory effect. The response to rIF-G varied from stimulation of some biopsies to strong inhibition of others. There was no similarity in the sensitivity pattern of the biopsies to rIF-A and rIF-G.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Transforming growth factor-beta 1 is a potent inducer of plasminogen activator inhibitor type-1 in human glioblastoma and carcinoma cell lines.

Transforming growth factor-beta 1 has been shown to suppress the urokinase activity in the glioblastoma cell line T-MG1 and the carcinoma cell line T-CAR1. The molecular mechanisms behind the decrease in the proteolyic activity is shown to be at least partly due to increased synthesis of plasminogen activator inhibitor type-1 and not by decreased synthesis of urokinase.

Blotting, Northern↗
PubMed1988

Amplification of the epidermal growth factor receptor gene in biopsy specimens from human intracranial tumours.

Amplification and overexpression of proto-oncogenes are associated with the malignant nature of some human tumours. In this study we have determined the prevalence of amplification of the proto-oncogenes c-erb B1 (= epidermal growth factor receptor gene), c-erb B2 and c-myc in 44 human intracranial tumours (27 gliomas, six metastases to the brain and 11 meningiomas). None of the tumours had an amplified c-erb B2 gene and only two tumours had an amplified c-myc gene. Nineteen per cent (five out of 27) of the gliomas, 50% (three out of six) of the brain metastases and 0% (0 out of 11) meningiomas had an amplified EGF-receptor gene. Amplification of the EGF-receptor gene appeared to give a growth advantage when single-cell suspensions of the tumours were grown in agarose.

Adult↗
PubMedDate not supplied

Amplification of the epidermal growth factor receptor gene in human gliomas.

Biopsy specimens of 19 human gliomas (10 glioblastomas, 2 anaplastic astrocytomas, 4 astrocytomas, one mixed glioma, one oligodendroglioma and one ependymoma) were examined for amplification of tumour-related genes located on chromosome 7: the proto-oncogene c-erb-B1 (encoding the epidermal growth factor receptor (EGFR], the proto-oncogene c-met, the platelet-derived growth factor A-chain gene, and the plasminogen activator inhibitor type-1 gene. Gene amplification was observed in 6 glioblastomas, and the EGFR gene was the only chromosome-7-gene examined that was amplified. The selective EGFR gene amplification in human glioblastomas suggests its potential role in the progression of some of these tumours.

Adult↗
PubMedDate not supplied

EGF-effects in vitro and in vivo on a carcinoma cell line rich in EGFR.

T-CAR1 is a human carcinoma cell line established from a brain metastasis. The tumour cells overexpress EGFR and contain an amplified EGFR gene. In vitro in the presence of 5% human serum the tumour cells grow as adherent cells in monolayer. Shortly after exposure to EGF a large number of tumour cells round up and detach, whereas some remain adherent. At the same time a redistribution of actin occurs. Cytochalazin B prevented this reaction, which indicates that actin is involved in the detachment of the tumour cells. The EGF-detached tumour cells however, did not differ from the tumour cells which remained adherent after EGF-exposure with regard to parameters such as growth in soft agar, growth response to EGF, tumour necrosis factor-alpha, interferon-gamma, and carmustin (BCNU), level of EGFR gene expression and EGFR gene amplification, S-phase fraction, and amount of DNA. It was speculated whether the EGF-induced cellular detachment in vitro could be correlated to metastatic potential in vivo or not. In order to address this issue, in vivo studies with subcutaneous T-CAR1 tumours in nude mice were performed. Administration of EGF resulted in growth stimulation in contrast to growth inhibition in vitro, whereas no effect of EGF on the metastatic potential was observed. Thus, the EGF-mediated tumour cell detachment seems to be restricted to in vitro conditions only.

Actins↗
PubMedDate not supplied

Lhermitte-Duclos disease and giant meningioma as manifestations of Cowden's disease.

A 43-year-old man with synchronous occurrence of Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum) and a giant meningioma with subcutaneous infiltration is reported. Subsequent examinations revealed typical manifestations of Cowden's disease (multiple hamartomaneoplasia syndrome), i.e. mucocutaneous lesions and increased head circumference. Our findings support the view that there is a correlation between Lhermitte-Duclos disease and Cowden's disease. We conclude that all patients with Lhermitte-Duclos disease should be thoroughly examined with regard to Cowden's disease, which necessitates lifelong follow-up with screening for neoplasia in various organ systems. The occurrence of both Lhermitte-Duclos disease and a meningioma as part of the Cowden's symptom complex is very rare and to our knowledge only one case with this combination of lesions has previously been reported.

Adult↗