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Biomedical subjects

K Wayss

Publications and source records attributed to K Wayss.

At least 19 recordsLinked to original sources

Experimentally induced infection with autonomous parvoviruses, minute virus of mice and H-1, in the African multimammate mouse (Mastomys coucha).

To determine whether the multimammate mouse (Mastomys coucha) could be used to evaluate rodent parvovirus-based vectors, neonates were subcutaneously inoculated with minute virus of mice (prototype strain, MVMp) or rat parvovirus H-1. The course of infection with both viruses was similar. Seroconversion occurred within two weeks after virus inoculation, as detected by use of hemagglutination-inhibition assays, and antibody titers remained high for the entire observation period of 12 months. Viral DNA and infective virions were detected in several organs of inoculated animals prior to seroconversion, as measured by use of Southern blotting and plaque assays, respectively. Infective particles subsequently became undetectable, whereas viral DNA imprints persisted in distinct organs for at least nine months. Clinical signs of parvovirus infection appeared around six weeks after virus inoculation, and consisted of hemorrhages, stunted growth, and transient hair color changes. Sudden death occurred in a significant fraction of animals infected with MVMp, but not H-1 virus, at the time of weaning. Altogether, MVMp, which is innocuous to its natural host, the mouse, and H-1 virus, which is poorly pathogenic to the rat, appear to be pathogenic for Mastomys coucha.

Animals↗

[Angiogenesis of human breast cancers: neovascularization in xenotransplants and oxygenation in situ in patients].

OBJECTIVE: Recent reports have shown that vascularization of breast cancers is an independent prognostic parameter. Tumor growth and neovascularization were investigated in xenotransplants of breast cancers and tissue oxygenation was measured in patients with breast tumors. METHODS: Tumor cells of the breast cancer MX-1 were implanted intradermally in 40 nude mice. Tumor growth and neovascularization were quantified microscopically. Tissue oxygenation was determined in 66 patients with breast tumors using the pO2-histography technique. RESULTS AND CONCLUSION: The angiogenesis begins prior to tumor growth, is insufficient and leads to chaotic blood flow. This results in a heterogeneity of tissue oxygenation in breast cancers. Oxygenation at the tumor periphery appears to be of prognostic importance for clinical outcome of breast cancer.

Animals↗

Activation of latent papillomavirus genomes by chronic mechanical irritation.

The skin of animals of a laboratory strain of Mastomys natalensis carrying endogenous, latent papillomavirus genomes was irritated by scratching with glasspaper. Hyperproliferation of the epidermis and amplification of viral DNA followed this treatment, and in approximately 27% of the animals virus-producing papillomas were induced.

Animals↗

Prognostic significance of DNA patterns and resistance-predictive tests in non-small cell lung carcinoma.

In a cooperative study, 240 surgical specimens of patients with non-small cell lung carcinomas (NSCLC) were investigated by means of flow cytometry, xenotransplantation to athymic mice and, an in vitro short-term test for predicting resistance. Aneuploidy was found in 83% of the tumors, and 20% showed more than one aneuploid DNA stemline. Patients with both aneuploid tumors and tumors with more than one DNA stemline had a significantly shorter survival rate than those with only diploid or only one DNA stemline. Patients whose tumors showed a low G0/G1-cell proportion or a high proliferation pool (S and G2/M-cell proportion) died earlier. A relationship could not be discerned between growth of tumors in nude mice or establishment of cell lines and the prognosis for the patients. Patients with in vitro-resistant tumors died earlier under chemotherapy than those with in vitro-sensitive tumors. Patients treated by radiation survived longer if the tumors were resistant in vitro. Thus, DNA patterns and in vitro short-term tests for predicting resistance represent useful tools for prognostic evaluation of patients with NSCLC.

Adult↗

DNA distribution in non-small-cell lung carcinomas and its relationship to clinical behavior.

A study of 187 surgical specimens of tumors of patients with non-small-cell lung carcinomas was carried out by means of flow cytometry. Eighty-four percent of the tumors were classified as tumors with abnormal DNA stemlines (DNA aneuploidy). Patients with tumors demonstrating DNA aneuploidy had significantly shorter survival times than those with tumors demonstrating DNA diploidy (p = .009). Cell cycle analysis was possible in 122 tumors. Patients whose tumors had 0-8% S-phase cells died later than patients whose tumors had 9-16% S-phase cells (p = .018). In addition, patients with tumors with a low fraction of labeled S-phase cells (autoradiography) had a better prognosis than patients with tumors with a high proportion of labeled S-phase cells (p = .041).

Adenocarcinoma↗

Sequential methotrexate (MTX) and 5-fluorouracil (FU) in human tumor xenografts.

Human and animal tumor-lines heterotransplanted in nude mice were treated with MTX and FU sequentially. In order to investigate the relationship between tumor response and drug toxicity sequence, time and dose of both MTX and FU were varied. Pretreatment with MTX followed by FU with intervals of 3 or 24 h produced superior therapeutic results when compared to single administration of MTX or FU, simultaneous treatment, or the reverse sequence. In the MTX followed by FU regimen, dose reduction of either MTX or FU tended to decrease the anti-tumor effect. To investigate the toxic effects of different regimens, tumor-free nude mice were treated with MTX and FU the same way as the tumor-bearing animals. In this case, toxicity (weight loss, leukopenia) was more pronounced in those schedules with the best therapeutic results. However, toxicity appears to be more clearly related to the applied FU-dose.

Animals↗

Growth of human bronchial carcinomas in nude mice.

Two hundred and thirteen lung tumours of primary site and 42 metastases were heterotransplanted into nude mice with an overall success rate of 44%. There were differences in success between the histological types. Squamous cell and adenocarcinoma had the highest success rate (51% and 43%, respectively) whereas large cell and small cell carcinoma had a lower success rate (38% for both). The average volume doubling times in the first passage in nude mice ranged from 8.2 in large cell carcinomas to 18.9 days in adenocarcinomas. In subsequent passages an increase in growth rate was found, the overall average doubling time falling from 14.5 days in the first passage to 7.1 days in the second passage. In a study with 171 non-small cell lung carcinomas (NSCLC), the growth data in nude mice were correlated with the clinical data of the corresponding patients. A relationship between the growth parameters in nude mice and prognosis of patients could not be found.

Adenocarcinoma↗

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.

Animals↗

Polysomal polyadenylated RNA and albumin messenger RNA in Mastomys liver and in a chemically induced hepatocellular carcinoma.

A hepatocellular carcinoma line (H78) was established from a primary liver tumor induced in Mastomys natalensis by a single administration of dimethylnitrosamine. Six to 8 months after transplantation (passages 5 to 7), well-differentiated tumors, still containing glucogen-storing cells, were isolated and used for the preparation of RNA. Polysomal polyadenylated RNAs from Mastomys liver and from H78 tumor line were then compared by hybridization kinetics. Total kinetic complexities were 6.6 X 10(9) and 6.3 X 10(9) daltons for liver and tumor, respectively. Complexities of the high and middle abundant class were reduced in the hepatoma. Heterologous hybridization reactions revealed that, in terms of RNA mass, all or most of the polysomal polyadenylated RNA present in the liver was also present in the tumor and vice versa. However, shifts in the relative abundance of messenger RNA sequences were detected. In contrast to most other transplanted hepatomas, H78 has approximately the same content of albumin messenger RNA on its polysomes as has untreated liver.

Albumins↗

Chemical carcinogenesis by the two-stage protocol in the skin Mastomys natalensis (Muridae) using topical initiation with 7,12-dimethylbenz(a)anthracene and topical promotion with 12-0-tetradecanoylphorbol-13-acetate.

The long-term (34 weeks) topical administration of 7,12-dimethylbenz(a)anthracene (DMBA) to the skin of male and female Mastomys induced a broad spectrum of benign and malignant tumors in all animals treated. In a two-stage carcinogenesis experiment with topical initiation with DMBA and topical promotion with TPA, 50% of the animals developed both benign and malignant skin tumors. In general, benign tumors occurred between weeks 15 and 25, whereas malignant tumors were seen 40 weeks after initiation. In contrast to the situation in Mus musculus, the benign tumors consisted mainly of keratoacanthomas instead of fibroepitheliomas. In the non-initiated, TPA-treated, control group four benign and four malignant tumors were seen, whereas animals of the DMBA-initiated, acetone-treated control group were free of tumors. The promotion of virus transformed cells with TPA is discussed.

9,10-Dimethyl-1,2-benzanthracene↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

[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.

Animals↗