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J Mattern

Publications and source records attributed to J Mattern.

At least 109 records · Page 6Linked to original sources

An alternative assay system for the detection of transforming genes.

We have developed an alternative assay system based on DNA mediated gene transfer (DMGT) for the detection of functional transforming genes which we find more sensitive and reliable than other assay systems. This approach involves selecting in tissue culture for cells which are expressing a drug-resistance marker co-transferred with the tumour DNA thus isolating the small number of cells which have taken up and are expressing exogenously added DNA. The ability of transformed cells present in this drug-resistant cell population to form tumours in athymic (nu/nu) nude mice was then used to assay for transforming genes. Using NIH3T3 and Rat 2 cells as recipients, tumours produced after DMGT with DNA from non-tumorgenic cells were only very rarely observed. Tumour induction was observed using DNA from a biopsy of a human ovary carcinoma and a spontaneous murine lung carcinoma. Two human retinoblastoma cell lines were negative for tumour induction. The transforming gene from the ovarian carcinoma was identified as c-K-ras2.

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Preclinical evaluation of diethoxy-(1-phenyl-1,3-butanedionato) titanium (IV) in human tumour xenografts.

The antitumour activity of diethoxy-(1-phenyl-1,3-butanedionato)titanium (IV) (DBT) in comparison to cis-dichlorodiammine platinum (cisplatin, cis-DDP) and cyclophosphamide (CTX) against human breast, colo-rectal and lung tumour lines growing as xenografts in nude mice was investigated. The antitumour activities and toxicities of DBT and cis-DDP are comparable whereas CTX was the most effective agent.

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Effect of five antineoplastic agents on tumor xenografts with different growth rates.

The effects of cyclophosphamide (Cy), doxorubicin (Dx), cisplatin (DDP), melphalan (L-PAM), and vincristine (VCR) on various human and animal tumor lines with different growth rates, growing as xenografts in NMRI (nu/nu) mice, were studied. Two types of response were observed: For Cy and Dx, the response of the xenografts was negatively correlated with tumor volume doubling time (TD), indicating that rapidly growing tumors were more sensitive to these drugs than were slowly growing tumors. For DDP, L-PAM, and VCR, the effects were positively correlated with the TD, indicating that slowly growing tumors were more sensitive to these drugs than rapidly growing tumors. The data are discussed in relation to the effects of the drugs on proliferating and nonproliferating cells obtained with other cell lines.

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[Pretherapeutic detection of tumour resistance to cytostatic agents].

Malignant tumours--even when they are of similar localization and histological type--very often react differently to cytostatic treatment. In order to determine the sensitivity or the resistance of malignant tumours, various test systems have been developed over the past few years: a) tissue or organ culture, b) assay for clonogenic tumour cells in soft agar, c) short-term culture of tumour cells, d) heterotransplantation of tumour material to nude mice. Practicability and limits of these methods are compared on the basis of the correlation between predictive test results and clinical results.

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[Sensitivity testing of chemotherapeutic agents for ovarian and breast cancers--possibilities and limits of different methods and of their application (author's transl)].

Well-defined and individualised chemotherapy of human malignant tumours can be initiated with the aid of sensitivity tests for chemotherapeutic agents prior to treatment. The effectiveness of the specific cytotoxic agent can be determined by sensitivity testing. For these investigations three methods are available at present: 1. a short-term incubation method (biochemical assay). 2. an agar-cloning assay as a specific tissue culture method and 3. a heterotransplantation method with transplantation of tumour cells into thymus-aplastic animals. For routine clinical testing only the biochemical short-time assay and the agar colony assay are of practical significance. The test rates and growth rates in the two methods are composed. The in-vitro and in-vivo correlations of sensitivity testing of chemotherapeutic agents and resistance to chemotherapeutic agents in the different test systems show that the accuracy of prediction for the correct positive or correct negative result is 90%. These results are based on retrospective analysis. For the evaluation of the different prediction assays and for the evaluation of the clinical application of these methods only a randomised prospective therapeutic study can give the answers. However, this has not yet been carried out to date.

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Growth kinetics of human lung tumours in nude mice.

In order to investigate the growth characteristics of xenografts of human tumours in nude mice, we heterotransplanted 22 human tumours of the lung into nude mice. We noted growth in 11 of these tumours (50%). The histological appearance of most of the tumours growing in the first passage in nude mice was comparable with that of the donor tumours. In further passages, however, a progressive dedifferentiation was noted in many tumours, depending on their growth rate. With the aid of growth curves and cell cycle kinetics (FMF analysis) it is shown that the growth kinetics of these tumours is affected by the transplantation and that the growth rate of such xenografts in nude mie is different from that of the original tumour in the patient.

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In vivo and in vitro detection of induced resistance to daunorubicin in murine leukemia L 1210.

By treatment of the mouse leukemia L 1210 with daunorubicin (2 mg/kg per week) a tumour cell line was developed which was resistant to this cytostatic agent. The sensitive and resistant tumour cell line could be distinguished using an in vitro short-term test. Cross resistance could also be reliably detected by this method. In all cases, a good correlation was observed between the results of in vitro short-term tests and animal experiments.

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Therapy of solid Walker carcinosarcoma 256 with bleomycin after synchronization with hydroxyurea.

Rats with the solid Walker carcinosarcoma 256 were synchronized with hydroxyurea (6 x 50 mg/kg or 1 x 300 mg/kg body weight) and treated with bleomycin (32 mg/kg body weight) at different time points thereafter. Bleomycin clearly affects Walker carcinosarcoma cells at the G1/S boundary or in S-phase. The improvement in the results of bleomycin therapy after pretreatment with hydroxyurea can mainly be accounted for by the synchronization of the tumour cells.

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Studies on the specificity of tissue supernatants on the proliferation of liver in baby-rats.

Supernatants (105,000 g) prepared from extracts of liver and kidney were injected at different concentrations into 10 day-old rats and the resulting effects on 3H-thymidine incorporation in liver, kidney and lung were measured over a period of 24 hours. Incorporation in all three organs is inhibited by supernatants from both liver and kidney, with maximal activity between 12 and 18 hours after injection. Fractions prepared from liver supernatant by ultrafiltration and alcohol precipitation also showed no specific effect on liver cells. In order to test whether the activity of any factors in the supernatants is cell-cycle dependent, organs of baby rats were synchronized by two different procedures: a) injection of a 3.5% casein solution, b) injection of hydroxyurea (2 x 10 mg/kg body weight with an internal of one hour). Inhibitory effects were only observed when the supernatants were injected during the G1-phase of the target cells. Supernatants prepared in a similar way from other organs such as spleen, lung or heart also inhibited thymidine incorporation in casein-stimulated liver from baby rats. All of our investigations have therefore failed to find any indication of tissue-specific activity in these extracts.

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[Studies in vivo and in vitro on the influence of 5-fluorouracil and n'-(2'-furanidyl)-5-fluorouracil on the walker carcinosarcoma 256 in the rat (author's transl)].

We compare the effects of 5-fluorouracil and N'-(2'-furanidyl)-5-fluorouracil (Ftorafur) in vivo (tumor size) and in vitro ([6-3H]-deoxyuridine incorporation) on solid Walker carcinosarcoma of the rat. 5-Fluorouracil and Ftorafur have a dose-dependent effect on tumor size and on [6-3H]-deoxyuridine incorporation in vitro. The in vivo effects on tumor size are similar when the dose of Ftorafur calculated by its molecular weight is about 3 times higher than that of 5-fluorouracil. In vitro an about 650 times higher dose of Ftorafur is required to achieve a comparable reduction of [6-3H]-deoxyuridine incorporation in the tumor cells.

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[Irradiation of solid Walker carcino-sarcomas after synchronisation with hydroxyurea (author's transl)].

Sprague-Dawley rats with solid Walker carcino-sarcomas were synchronized with hydroxyurea (HU; 6 x 50 mg and 1 x 300 mg HU/kg body weight) and then irradiated at different time points (60Co). The synchronized tumors showed a significant delay of growth when irradiation was applied in the late G1 phase, at the transition G1/S and in the early S phase. The remaining phases of the cell cycle, especially the S phase showed the same sensitivity as the non-synchronized controls. Improvement of therapy by irradiation after HU application was largely due to the synchronization of tumor cells. Only the increased therapeutic effect of irradiation shortly after application of HU can be explained also by combination of both HU and irradiation.

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Determination of trace elements in peripheral lymphocytes from tumor-bearing rats.

Neutron activation analysis of peripheral lymphocytes from healthy and Walker 256 carcinosarcoma-bearing rats resulted in the quantitative determination of Co, Cu, K, Mn, Rb, Se and Zn, and a qualitative determination of Au and Sb. From corresponding plasma samples, Co, Zn, Rb, Se and Cs were analyzed. Differences in trace element concentrations could only be detected in plasma of tumor-bearing animals which showed a decreased Zn and Co content of 50% and 30%, respectively, and a rise of Rb when compared to plasma of control animals.

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