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.

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.

Melatonin circadian-stage-dependently delays breast tumor development in mice injected daily for several months.

Breast tumor incidence is compared in C3CF1 mice, receiving at one of 6 different circadian stages, daily injections of melatonin or of a vehicle or no treatment, the latter in a slightly cooler environment. Results are summarized when approximately 33% of all animals have a breast tumor. Vehicle treatment increases tumor incidence.

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.

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).

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.

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.

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.

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.

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.

[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.

[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.

Induction of a slowly growing transplantable adenocarcinoma metastasizing into the lungs.

In male Long Evans rats Dibutylnitrosamin induces adenocarcinomas of the lung. Transplantation of a tumor cell suspension prepared from the tumor leads in 100% of cases to death by metastases from adenocarcinoma of the lung after an average of 24 weeks when applied i.m.

[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.

[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.

Immune prophylaxis of experimental cancer by corynebacterium parvum.

Fractionated administration of C.p. i.

[Clinical experiences with Holoxan in small cell carcinoma of the bronchus (author's transl)].

Clinical experiences obtained until now in the treatment of 47 patients with small cell carcinoma of the bronchus with Holoxan are reported. Special emphasis is laid to the results of a prospective randomized study; two groups of patients, one of them undergoing Holoxan therapy, the other receiving symptomatic treatment, have been investigated in respect of relationship between tumour remission, quality of life and survival time.

[Therapy of inoperable bronchial carcinoma].

The results of a prospective randomized study on carcinoma of the bronchus are reported. In a total of 56 patients polychemotherapy, high-dosage vitamin-A treatment, Endoxan and immunotherapy, as well as the application of proteolytic enzymes in altogether 5 combinations of therapy were tested.

Active experimental inhibition of cancer by corynebacterium parvum.

It has been demonstrated that 5 microgram Corynebacterium parvum (Mérieux, Lyon) applied i.v. once weekly in mice of the strain C 3 H X Swiss Albino F 1 after three pregnancies effectively inhibits tumour growth.

Stimulation of immune response in lung cancer patients by vitamin A therapy.

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.