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Biomedical subjects

C Cerni

Publications and source records attributed to C Cerni.

At least 37 records · Page 2Linked to original sources
PubMed1987

Transfer of 'immortalizing' oncogenes into rat fibroblasts induces both high rates of sister chromatid exchange and appearance of abnormal karyotypes.

Cell lines established after transfer into FR3T3 rat fibroblast cells of 'immortalizing' oncogenes (plt gene (large T protein) of polyoma virus, v-myc gene of MC29 virus, rearranged forms of c-myc) exhibited increased rates of sister chromatid exchange (SCE). This was observed neither in cells which expressed one of the oncogenes responsible for the terminal stages of tumorigenic transformation (polyoma virus pmt (middle T protein), mutated ras genes), nor in cell lines carrying oncogenes of both types. Abnormal chromosome numbers were observed in cell lines expressing plt or myc, but not after transformation by pmt or ras oncogenes.

Animals↗
PubMed1987

Elevated expression of an exogenous c-myc gene is insufficient for transformation and tumorigenic conversion of established fibroblasts.

Two established rat fibroblast lines, differing only by their number of generations in culture, show dramatically different responses to the elevated c-myc expression delivered by an efficient murine c-myc retrovirus vector. Thus, a late passage (60 generation) FR3T3 line acquires a transformed and tumorigenic phenotype upon introduction of this activated c-myc gene as indicated by its altered morphology, high efficiency of focus formation, soft agar clonability, saturation density in monolayer culture, and short latency of tumorigenicity in syngeneic hosts. Remarkably, none of these characteristics, except for an increased refractility in monolayers and an epidermal growth factor (EGF)-dependent agar clonability, were observed in a variety of early passage (10 generation) FR3T3 c-myc clones. BALB/c A31 fibroblasts transfected with this c-myc retroviral vector behaved essentially the same as the FR3T3 early line except for their inability to grow in suspension in response to EGF. However, transformation and tumorigenic conversion of each of these three fibroblast lines was achieved by an activated ras oncogene. Hence, elevated c-myc expression is insufficient for transformation of established fibroblasts but depends upon other acquired cooperating functions which are not necessary for ras induced transformation. We also demonstrate that endogenous c-myc expression remains unaffected even in clones expressing a 100-fold excess of exogenous c-myc RNAs demonstrating that c-myc autoregulation is not operative in these cells.

Animals↗
PubMed1984

Effect of tissue culture variables on sister chromatid exchange in a nontransformed rat cell line.

The frequency of sister chromatid exchange (SCE) was determined in a nontransformed diploid rat cell line, FR3T3 , under several tissue culture variables such as cultivation temperature, growth conditions of cells, and concentrations of 5-bromo-2'-deoxyuridine (BrdU). The conclusions to be drawn from these experiments are: (a) The cell growth and mechanisms(s) of SCE formation in FR3T3 cells are largely temperature independent (or efficiently regulated) in the range between 33 and 40.5 degrees C. (b) The concentration limits for BrdU incorporation are 5 to 100 microM; baseline frequency is about 11 SCE/metaphase (constant up to 20 microM BrdU) and increases only moderately at higher BrdU concentrations. (c) Toxic levels of BrdU (150 microM) cause a decrease of SCE rates below that found at 100 microM, presumably due to selective cell death. (d) Keeping cells growth arrested over a long period causes substantial SCE induction after replating. (e) Induced increase of SCEs probably occurs in this manner during the first cell cycle after release from growth arrest. It is no longer detectable after the fourth consecutive cell division.

Animals↗
PubMed1984

Sister chromatid exchange in FR3T3 rat fibroblasts transformed by Simian virus 40.

The frequency of Sister Chromatid Exchange (SCE) was determined at low (33 degrees C) and high (40.5 degrees C) temperatures in cell lines derived from FR3T3 rat fibroblast cells after transformation either with Wild-Type Simian Virus 40 (SV40-WT), with an origin-defective SV40 (SV40-ori-), or with the early temperature-sensitive mutant tsA30. Of these cell lines, SV40-WT-, SV40-ori--, and one class of tsA30-transformants (A-type) express the transformed phenotype both at 33 and 40.5 degrees C. The other tsA30-transformants (N-type) revert to a normal phenotype at high temperature. As compared with normal FR3T3 cells, all transformants exhibited, at 33 degrees C, increased numbers of metaphases with high SCE rates. At 40.5 degrees C, all cell lines which expressed a transformed phenotype (SV40-WT, tsA30 type A, SV40-ori-) exhibited substantially increased SCE rates. That this increase was not related to a possible induction of viral replication by BrdU, was proven by Southern blot analysis and by SCE data on SV40-ori--transformed cells. By contrast, no such temperature-induced increase of SCE rates was observed in tsA30-transformants of type N.

Animals↗
PubMed1984

Increase of sister chromatid exchange formation induced by diethylstilbestrol.

The latent appearance of genital tract tumors in young women is highly correlated with prenatal exposure to synthetic estrogens such as diethylstilbestrol (DES). To extend the information on the mutagenic effect of DES, the frequency of sister chromatid exchange (SCE) was determined in bone marrow cells of Sprague-Dawley rats and in cultured FR3T3 rat fibroblasts. In this study a significant increase of SCE frequency after the application of different concentrations of DES could be observed both in vivo and in vitro.

Animals↗
PubMed1984

Chronic application of a tumor promoter to confluent nontransformed rat cells induces the irreversible expression of transformed phenotype.

The hypothesis was put foreward that 'immortalisation' of an established nontransformed cell line might represent one type of 'initiation' in the process of malignant transformation. Therefore, a nontransformed rat fibroblast cell line, FR3T3, was investigated as to whether or not it could be irreversibly transformed by exposure to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA was applied in different treatment schedules at varying growth phases of the cells (logarithmic or stationary growth). The cells' acquisition of transformation-associated properties was studied by means of various transformation assays (saturation densities and formation of dense foci both at low and high serum concentrations, as well as growth in agarose and production of plasminogen activator, PA). We found that a phase of stationary growth plus TPA treatment was decisive for the induction of transformed cell clones. Growth in 0.5% serum was used as the selection procedure. Several isolated foci manifested, in vitro, highly transformed phenotypes. However, only 1 of 12 clones produced PA. All cell lines derived from these clones, proved to be tumorigenic in syngeneic animals. Since the nontransformed, but 'immortal' rat cell line is susceptible (at certain growth conditions) to the tumor promoting activity of TPA, we conclude that induction of 'immortalisation' may, from an operational point of view, correspond to 'initiation', at least in this particular cell line.

Animals↗
PubMed1984

The transformation of a rat cell line induced by a tumor promoter occurs without affecting sister chromatid exchange.

Malignant transformation of cells of an established rat cell line, FR3T3, can be achieved by the exclusive treatment of the cells with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) over a stationary growth period. In the course of the transformation process, sister chromatid exchange (SCE) rates of treated cells were examined at various key-points and compared to control cells. It was found that neither a single TPA treatment nor repeated TPA application during 16-22 consecutive cell-doubling times (which induces substantial alterations of the phenotypes) increased SCE rates in the rat cells. Furthermore, transformed cell clones, which were selected from low-serum cultures and which were found to be tumorigenic in vivo, had SCE rates in the same range as the parental nontransformed FR3T3 cells. It is, therefore, concluded that malignant transformation of the rat cells - induced by TPA - occurs without affecting such large-scale DNA rearrangements as are detectable by means of the SCE method.

Animals↗
PubMed1983

Indication of reduced doxorubicin-induced cardiac toxicity by additional treatment with antioxidative substances.

The influence of antioxidative substances on doxorubicin-induced cardiac toxicity was studied in C 57 BL mice. Tocopherol (500 mg/kg), glutathione (1000 mg/kg), cysteamine (15 mg/kg) and L-cysteine (1000 mg/kg), injected i.p. 24 h before doxorubicin treatment (15 mg/kg i.p.) were able to reduce malonaldehyde production in cardiac tissues significantly. SH-containing substances with high reducing activity, such as vitamin E, could be a useful tool in clinical trials to prevent doxorubicin induced cardiac damage.

Animals↗
PubMed1983

Lymphocyte transformation and isovolemic hemodilution with hydroxyethylstarch 450,000.

The effect of hemodilution upon lymphocyte transformation was studied in vivo. 20 p.c. of circulating blood volume was replaced by Hydroxyethylstarch 450,000 6%, (HES 450) and 24 hours later but prior to surgery lymphocyte transformation using PHA was not substantially changed. These findings were in accord with previous in vitro studies. There appeared to be no significant change of the total lymphocyte count, alteration of serum proteins seemed to be proportional presenting a mere dilutional phenomenon. It can thus be concluded that hemodilution does not impair cellular immune defense nor increase the risk for patients prone to sepsis or spread of malignancy.

Blood Cell Count↗
PubMed1983

[Effect of dextran 60,000(D 60) and hydroxyethyl starch 450,000 (HES 450) on lymphocyte transformation].

Lymphocytes of volunteers were recovered, isolated and H3 thymidine incorporation was measured in the presence of D 60 and HES 450 with and without PHA. Without mitogen dextran caused only a marginal increase of incorporation whereas HES brought about no change. When PHA-stimulation was used, both compounds seemed not to influence H3-thymidine incorporation. It is concluded that in vitro even in molar concentrations corresponding to clinical haemodilution these solutions appear not to suppress lymphocytic activity.

Adult↗
PubMed1982

The detection and measurement of oncodevelopmental proteins in gynecological malignant disease.

Data from the literature and our own measurements with alpha-fetoprotein (AFP), carcinoembryonal antigen (CEA), alpha 2-pregnancy-associated globulin (alpha 2-PAG), human chorionic gonadotropin (HCG), human placental lactogen (HPL) and pregnancy-specific beta 1-glycoprotein (SP-1) are related to clinical data. Only AFP in endodermal tumors and HCG in germ cell carcinomas can be used for clinical monitoring.

Carcinoembryonic Antigen↗
PubMed1982

[Results of a comparative therapy study for inoperable lung cancer].

In a prospective randomized study 78 selected patients with bronchogenic cancer have been included, and five different treatment modalities have been compared (1. Biologic therapy; 2. Vitamin A + Cytoxan; 3. Vitamin A + Telecobalt irradiation; 4. Telecobalt irradiation; 5. Immunotherapy). No significant differences if survival times between the different groups have been observed. Nevertheless, significant differences of survival times were found between small cell and squamous cell carcinoma patients without respect to the therapy applied. The highest number of remissions was obtained by therapy 3, followed by 4 and 2. Consequences for further studies are discussed.

Adult↗
PubMed1981

Failure of somatostatin to influence experimental tumor cell growth in vivo and in vitro.

The influence of somatostatin on tumor cell growth was studied in vivo in mice (sarcoma 180 ascites tumor and Lewis lung tumor) and in vitro on nontransformed and polyoma-transformed cell lines. 4 or 20 micrograms/100 g of cyclic somatostatin and 4 micrograms/100 g of linear protamin Zn-bound somatostatin were injected s.c. twice daily in the in vivo study. Cyclic somatostatin (1, 4 or 10 micrograms/ml) was added twice daily to the cell cultures. Somatostatin administration influenced neither the survival of animals nor the growth rate of cultured cell lines.

Animals↗
PubMed1980

[Aminopenicillin rashes - a multicentric prospective study (author's transl)].

538 patients, admitted to the hospitals participating in this study for a variety of indications for antibacterial therapy, were treated by the ampicillin-analogue Epicillin. 42 patients (7.8%) who developed exanthem underwent detailed clinical and immunological investigation. Exanthems were scored according to the form of application and doses of Epicillin as well as to the morphology and time of onset of the exanthem. A variety of serological tests were performed: 1. total IgE (RIST), 2. presence of penicilloyl-specific IgE (RAST), 3. penicilloyl-reactive antibodies using an antiglobulin-haemagglutination-tests. In addition, PHA-induced lymphocyte transformation was studied in 10 patients with exanthems. 38/42 patients developed transient monomorphic morbiliform or scarlatiniform exanthems. 4. exanthems were classified as urticarial or polymorphic. In contrast to the 38 patients, the latter also were positive in the serological tests as it is observed in patients with IgE-mediated penicillin allergy.

Ampicillin↗
PubMed1979

[The leukocyte migration inhibition test (LMIT) in recurrent herpes simplex labialis. Comparison of the results of treatment with BCG and Levamisole (author's transl)].

Forty six patients suffering from recurrent herpes simplex labialis (HSLR) have been treated by either BCG or Levamisole. Therapy was equally successful in both groups: 10 patients remained free of symptoms during the observation period, 11 patients improved clearly and 2 patients did not respond to the therapy. Sensitization of lymphocytes toward herpes simplex virus antigen (HVS-AG) was determined in vitro by means of the leukocyte migration inhibition test (LMIT); test were performed before therapy and in certain intervals after the end of it. While lymphocytes of 10 control persons could be stimulated by HSV-AG, those of patients suffering from HSLR did not react to this antigen before onset of any therapy. Clinical success of therapy correlated well with the in vitro results of the LMIT: after therapy, the lymphocytes of symptom-free and improved patients also reacted in vitro to the antigen added.

Adolescent↗