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Biomedical subjects

H Wrba

Publications and source records attributed to H Wrba.

At least 19 recordsLinked to original sources

Carcinogenicity testing of some constituents of black pepper (Piper nigrum).

In mice, injection of safrole, tannic acid or methylcholanthrene (MCA) during the preweaning period induced tumors in different organs. Safrole and tannic acid (constituents of black pepper) were weak carcinogens when compared with MCA which was used as a carcinogenic control substance. Force feeding of d-limonene (one of the pepper terpenoids) for a long time to the mice which were injected with any of the above 3 substances reduced their carcinogenic activity, while force feeding of piperine (one of black pepper alkaloids) was ineffective.

Alkaloids

Carcinogenesis induced by black pepper (Piper nigrum) and modulated by vitamin A.

Painting and feeding of mice with 2mg of an extract from black pepper on 3 days a week for 3 months results in a significant increase of the number of tumor-bearing mice. Tumor incidence is reduced in those groups of experimental animals receiving 5 or 10mg Vitamin A-palmitate twice weekly for 3 months by feeding or painting during and subsequent to application of pepper extract. Feeding of mice with powder of black pepper in diet (50g/3kg food) has no impact on carcinogenesis.

Administration, Oral

Prevention of 3-methylcholanthrene-induced skin tumors in mice by simultaneous application of 13-cis-retinoic acid and retinyl palmitate (vitamin A palmitate).

Two retinoids (13-cis-retinoic acid and retinyl palmitate ) have been shown to exert a good preventive effect in chemically induced papillomas and carcinomas of the skin in female Swiss mice; this effect was investigated over a period of 23 weeks. The tumors were induced by repeated topical application of 3-methylcholanthrene (0.3% MCA, dissolved in acetone; 14 applications). Retinyl palmitate (RP; 6 mg in 0.1 ml acetone/mouse; 10 applications) and 13-cis-retinoic acid (RA; 3 mg in 0.1 ml acetone/mouse; 10 applications) were also administered topically for the 3rd to 9th week from the start of the experiment. This investigation gave evidence for the fact that both the retinoids did not only inhibit the development of skin papillomas but had also a marked effect on skin carcinomas.

Animals

Prevention of transplacentally induced malignant diseases.

Administration of vitamin A (retinol palmitate) causes a reduction of transplacentally induced leukemias. Subsequent to a transplacental application of ENU, addition of vitamin A as a suspension to drinking water leads to a reduction of leukemia incidence to 50% as well as to a corresponding decrease of this disease as a cause of death. Yet there is no influence of vitamin A on the adenomas of the lung arising in this experimental design.

Animals

Experimental cancer prophylaxis.

In A-Jax mice, the appearance of MCA-induced sarcomas in delayed by Vitamin A application. Continuous uptake of drinking water containing 0.05% of a retinol palmitate emulsion leads to a significant inhibition. Administration of ethylnitrosourea (ENU) to pregnant Swiss mice on the 17th day of gravidity results in the formation of lymphoblastoid leukemias from the beginning of the 12th week after birth, 90% of the animals dying within 25 weeks. In this case, continuous addition of 0.1% retinol palmitate emulsion to drinking water leads to a dramatic reduction of the tumor risk to about 50%. By additional administration of proteolytic enzymes of animal and plant origin this risk can be further reduced. The lung adenomas developing to 100% in the animals are not influenced by this treatment. Vitamin A, added to drinking water, exerts a strong inhibitory effect on transplacentally induced leukemia.

Adenoma

Delay of diethylnitrosamine-induced hepatoma in rats by carrot feeding.

Carcinogenesis and death caused by diethylnitrosamine(DENA)-induced hepatomas in Sprague Dawley rats can be significantly delayed by feeding only carrots for several days a week. As this result is not obtained by supplementing food with even higher concentrations of synthetic beta-carotene, there must be several other factors which--together with the carotenoid--contribute to the positive effect. Several other possibilities such as effects of fasting, direct interactions with the carcinogen, resorption, vitamin A storage in the liver, etc., are proposed and discussed.

Animals

Establishment of slowly growing lung tumor cell model by aspiration of tumor cells.

In male BDF1 mice, aspiration of suspended Lewis lung tumor cells at a certain concentration leads to the occurrence of lung carcinomas after 30 days. Under the chosen experimental conditions tumor incidence is about 70%. Within 20 days, animals die from this slowly growing tumor. Furthermore, the experimental conception offers a model which seems suitable for investigations into growth regulation of lung tumors.

Animals

Influence of vitamin A on the formation of ethylnitrosourea (ENU)-induced leukemias.

In mice, administration of ethylnitrosourea (120 mg/kg body weight) on day 14 of pregnancy leads to a transplacentally induced and transplantable leukemia in a high percentage of the offspring. Moreover, 100% of the offspring develop, later on, adenomas of the lung. Application of retinol palmitate (daily dose 170,000 IU/kg) reduces leukemogenesis up to 50%, yet without influencing formation of lung adenomas.

Adenoma

Augmented immunogenicity of Lewis lung carcinoma by infection with herpes simplex virus type 2.

In vitro, LLT cells sustain HSV-2 replication without evidence of lysis. Simultaneously, multiplication of the cells is stimulated. These xenogenized cells were tested for their immunopotentiating capacity: three-step immunization with xenogenized viable cells conferred significantly augmented transplantation resistance to a challenge graft with 4 x 10(4) intact LLT cells. Latency periods preceding tumor formation were increased and 15% of the mice failed to form primary tumors. Metastasis was likewise decreased and 25% of the mice had healthy lungs. Immunopotentiation, however, did not suffice to significantly protect against a challenge with 6 x 10(4) intact cells. The presence of virus-specific neoantigens on HSV-2-infected viable cells was demonstrated by the progressively increasing number of rejections of 4 x 10(4) xenogenized cells during the successive immunization steps. Immunization with non-viable LLT cells did not augment resistance to challenge.

Animals

[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

[Ifosfamide versus ifosfamide + CCNU in the treatment of inoperable small cell carcinoma of the lung. A clinical study].

55 selected patients with inoperable small cell carcinoma of the lung have been induced in a randomized prospective trial in order to compare the efficacy of ifosfamide monotherapy with the combination of ifosfamid + CCNU. Initially a control group, treated with symptomatic therapy only, was also included but preliminary analysis revealing that results were unfavourable in comparison to those of the chemotherapy group; this treatment arm was omitted. 53 of 55 patients were evaluable. In group 1 (symptomatic therapy) results were better as to patients' quality of life, but no tumor remissions have been observed and survival times were significantly shorter (15 to 122 days; geometric mean 42.35 days). In group 2 (ifosfamide monotherapy) one total remission (lasting 15 months) and 2 partial remissions (lasting from 3 weeks to 4 months) have been achieved; in this group survival was 3 to 473 days (geometric mean 110.15 days). In group 3 (ifosfamide + CCNU) 7 partial remissions have been observed (3 weeks to 4 months), survival was 17 to 477 days (geometric mean 107.32 days). The combination of ifosfamide with CCNU did not reveal any advantage in comparison to ifosfamide monotherapy.

Adult

Immune prophylaxis of experimental cancer by corynebacterium parvum.

Fractionated administration of C.p. i.v. in mice at risk from sarcomas after injection of 0.2 mg MCA leads to a significant prolongation of the period of latency under certain circumstances. Experimental groups which have received the immune stimulator for 6 weeks immediately after the cancerogenic factor show the best results. After tumour manifestation there is no perceptible preventive effect of C.p.

Animals

[Immune stimulation with vitamin A therapy in patients with pulmonary neoplasms].

Based on a clinical trial, in which patients with unresectable bronchogenic cancer were treated with a combination of vitamin A plus chemotherapy, or vitamin A plus radiotherapy, a study was initiated in which vitamin A alone was given for tumor treatment. 9 male patients with metastatic unresectable squamous cell carcinoma of the lung were treated with vitamin A palmitate or 13-cis vitamin A acid. Up to seven treatment courses were given during a period of 60 weeks. Through weekly evaluation of the patients' immune status, an immune potentiating effect of the vitamin A therapy could be demonstrated. An increase of lymphocyte blastogenesis response to PHA which is significant (p less than 0.001) compared with the pretreatment values, was found in all patients at the end of one vitamin A treatment course. Increased delayed cutaneous hypersensitivity reactions were observed also in all patients. The immune potentiating effects of vitamin A therapy, as well as the demonstrated direct effect on the tumor, introduces a wide range of combination therapies.

Carcinoma, Bronchogenic

[Risk of lung cancer and "smoker's prophylaxis" in Austria].

The smoking habits of the Austrian population and their significance for the development of effective smoking control programmes are reported. An increasing trend in the consumption of cigarettes with a lower content of tar and nicotine can be observed as well as a slight reduction of lung cancer death-rates in Austria. An analysis shows that, at present, only the younger male age groups show a decrease of lung cancer risk. Possible relations of these findings to the improvement in the quality of cigarettes are discussed, namely the reduction in the amount of carcinogens.

Adult