Zeitschrift fur Krebsforschung und klinische Onkologie. Cancer research and clinical oncology最新文献

In the genetically determined pigment cell tumors of platyfish and platyfish-swordtail hybrids, the degree of malignancy of pigment cells which have been neoplastically transformed by a tumor gene (Tu) depends on the type and number of certain regulating genes (R). In the present study, the tyrosinase activities in tumors of different degrees of malignancy (black spots, premelanomas, melanomas) have been determined. The results demonstrate a close correlation between the level of tyrosinase activity and the degree of malignancy. Spot patterns consisting of completely differentiated (benign) Tu-transformed cells show no tyrosinase activity. Premelanomas containing a few incompletely differentiated (malignant) Tu-transformed cells in addition to many differentiated ones show moderate tyrosinase activities. Melanomas which contain increasing numbers of incompletely differentiated cells with increasing growth rates show high to extremely high tyrosinase activities. Thus, the tyrosinase levels present in these tumors can be used as an indicator for the degree of differentiation and, thereby, for the degree of malignancy of the neoplastically transformed pigment cells.

46 samples of commercially available diets for experimental animals have been analysed for their content of volatile N-nitrosamines by use of a nitrosamine-specific detection method (TEA-detector). 80% of all analysed samples were positive for N-nitrosodimethylamine with a maximum content of 79 ppb (microgram/kg) found in one sample. 59% of the samples were positive for N-nitrosopyrrolidine with 26 ppb as highest content. In 3 samples trace quantities (less than 1 ppb) of N-nitrosodiethylamine were found, one sample contained N-nitrosopiperidine (4 ppb).

The biological effect of N-nitroso-N-methyl-N-dodecylamine (NMDA) was examined in Syrian hamsters as part of a comparative study. Data obtained show that after intragastric administration of NMDA, the urinary bladder was the main target organ for the carcinogenic effect. Transitional cell neoplasms developed and a positive dose response relationship was observed. Lung tumors occurred only in female hamsters, whereas males more frequently showed neoplasms of the nasal cavity and digestive tract.

49 patients with disseminated bronchogenic carcinoma (small cell, 16;squamous cell, 17;large cell, 12;adeno, 4) were treated with a combination of adriamycin, cyclophosphamide, vincristine and DTIC. In a randomized series (21 patients) chemotherapy alone was compared to chemotherapy plus heparin. Partial remission was achieved in 8 patients with small cell carcinoma, in 5 patients with large carcinoma and in 2 patients with squamous cell carcinoma. The survival of patients who responded to therapy was greater than the survival of patients who did not respond to therapy. The duration of remission and the survival time was not longer in patients who had additional heparin therapy.

The inoculation of Ehrlich ascites carcinoma cells in irradiated and cortisone-treated rats induced an ascitic tumor and lymph node metastases. Chromosome banding analysis showed that metastatic lymph nodes are composed of Ehrlich tumor cells and normal rat metaphases, derived from reactive host cells.

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG), or its derivatives N-hexyl-N'-nitro-N-nitrosoguanidine (HNNG) and 1,6-bis(N'-nitro-N-nitrosoguanidinyl)-n-hexane (HxBNNG) were given to newborn ICR/JCL mice by a single subcutaneous injection in 1% gelatin suspension. In an acute toxicity study, the maximum tolerated dose of MNNG, HNNG or HxBNNG was 62 microgram/g, 555 microgram/g, or 500 microgram/g of body weight, respectively. In a chronic study, a single subcutaneous injection of MNNG to newborn mice at a dose of 62, 31, or 3 microgram/g of body weight induced tumors of the lung and hemangioendotheliomas in both sexes, and tumors of the liver in males. Other pathologic findings, such as deformities of the spine and alopecia of the skin, were frequently observed. The incidences of tumors in each group were clearly dose related. HNNG and HxBNNG were not tumorigenic within the observation period.

Two 8-month-old and two 4-month-old male beagle dogs received 250 ml of 150 microgram/ml solution of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and 2% Tween 60 mixed with a pellet diet twice a day for 8 months as the same methods used for mongrel dogs in our first report [Juntendo Medical Jouranl 19, 579-583 (1973)]. Gastric carcinomas with distant lymph nodes metastases occurred in three beagle dogs except for one died from anesthesia at the endoscopy. Metastases to the liver were observed in two beagles. In the most long-lived beagles, peritonitis carcinomatosa with ascites and metastases to the liver, lungs, bones, and skin were found. Main gastric tumors were located at the subcardia in two dogs (elevated tumor in dog No. 6, ulcerated tumor in dog No. 8), but in dog No 7 at the angulus (ulcerated tumor). Histologically, carcinomas were composed of poorly differentiated adenocarcinoma, signet-ring cell carcinoma, tubular adenocarcinoma, and undifferentiated adenocarcinoma. In all of three dogs which developed adenocarcinoma of the stomach, Stewart's criteria were completely satisifed. Using our methods the target organ is limited only to the stomach, without any sarcomatous lesion of the intestines.

The effect of 1-oxopropylpropylnitrosamine (1-OPPN) was examined in Syrian hamsters. The subcutaneous (s.c.) LD50 was 308 mg/kg b.w. Animals treated s.c. once with a high dose of 1-OPPN had subcutaneous sarcomas and vaginal papillomas. Weekly s.c. injections for life led to high incidences of sarcomas at the injection site. In addition, 1-OPPN had a systemic effect. Neoplasms developed in the nasal cavity, larynx, trachea, lungs forestomach, and vagina. The results are discussed in connection with those found with other DPN derivatives substituted in the alpha-position.

The carcinogenicity of the alpha-dipropylnitrosamine (DPN) methyl-ether, 1-methoxypropylpropylnitrosamine (1-MPPN), was investigated in Syrian hamsters for comparison with the effect of the alpha-DPN acetylester, 1-acetoxypropylpropylnitrosamine (1-APPN). It seemed possible that 1-MPPN, 1-APPN and DPN could form a common intermediate. However, contrary to the effect of 1-APPN, no tumors were found at the injection site after subcutaneous 1-MPPN treatment. The main target organ for 1-MPPN was the respiratory tract (as with DPN) and the lungs were greatly affected. In addition, pharyngeal and forestomach tumors occurred, and these were not observed after DPN administration. The results of 1-MPPN treatment, relative to DPN and 1-APPN, are discussed.

Pregnant Syrian golden hamsters were treated with a single intra-peritoneal injection of ethylnitrosourea (ENU) solution a few hours pre-parturition. Offspring either received no further treatment or from 6 weeks of age, bi-weekly application of ENU solution in acetone for 20 consecutive weeks. Progeny from non, transplacentally treated mothers were also treated topically. Among all treated groups, 8.6% of the animals developed pigmented skin tumors, most of these animals having received the combined treatment. This group also showed a significantly decreased latency period in females compared to males. One of the skin tumors, which was histologically and clinically benign, was transplanted several times and subsequently exhibited malignant features.