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

Disulfiram (DSF) delayed the appearance of diethylnitrosamine (DEN)-induced strand breaks in liver DNA of rats. The fragmentation of liver DNA produced by DEN was studied 4 and 24 h after administration of the carcinogen on alkaline sucrose gradients. A single dose of 500 mg/kg DSF given 1 h prior to carcinogen treatment delayed for at least 4 h the DEN--induced strand breaks in liver DNA. A single DSF pretreatment, however, did not protect against carcinogen-induced strand breaks when observed 24 h after DEN injection. It is possible that continuous administration of DSF might inhibit the DEN-produced damage of the genetic material.

Mononuclear phagocytes in tumors cannot be reliably identified and quantified using morphological criteria alone. For this reason an alternative method, which depends on functional properties is described: Macrophages and monocytes derived from tumors from rosettes with antibody-coated sheep red blood cells and can thereby easily be detected and differentiated from tumor cells.

Several benign and malignant tumors of bone and cartilage were examined by means of type-specific collagen antibodies in connection with indirect immunofluorescence technique in order to determine wether there is a positive correlation between cell morphology and gene expression as refered to the synthesis of tissue- or cell-specific collagen. In general benign bone and cartilage tumors show the collagen type corresponding to the original maternal tissue. In malignant osteogenic tumors a strong positive correlation was found between morphologic differentiation of osteosarcoma cells and tissue specific collagen synthesarcomas. Unrelated to the grade of differentiation and the type of malignant tumor, collagen type III could be demonstrated in all tumors investigated, occurring rather from vascular stroma than from the tumor cell itself.

4-Methylphenylhydrazine hydrochloride was administered as 10 weekly subcutaneous injections of 140 microgram/g body weight and as 7 weekly intragastric instillations of 250 microgram/g body weight in physiological saline to randomly bred Swiss mice. Treatments given subcutaneously resulted in induction of lung tumors in incidences of 36% in females and 44% in males, while intragastric treatment caused a 40% incidence in females. In addition, it gave rise to blood vessel tumors by intragastric route in incidences of 32% in females and 18% in males. In the two physiological saline-treated control groups, the lung tumor incidence (combined) was 20% in females and 21% in males, while the blood vessel tumor incidence (combined) was 7% in females and 6% in males. Histopathologically, the lesions were classified as adenomas and adenocarcinomas of the lungs, and angiomas and angiosarcomas of blood vessels. 4-Methylphenylhydrazine was postulated to be a metabolite of 4-hydroxymethylphenylhydrazine, an ingredient of the commonly eaten mushroom Agaricus bisporus. The implications are discussed with respect to the tumorigenesis data.

Twenty-four patients with far advanced malignant tumors, resistent to established chemotherapy,, were treated with the combination of MNU and Cyclophosphamide. The drugs were administered in six-day cycles sequentially. MNU in doses of 4 mg/kg body weight and Cyclophosphamide in doses of 8 mg/kg body weight were given. Results of treatment showed response (greater than 50% tumor regression) in 10 (42%) of the 24 treated patients. Seven remissions were complete and three partial. Patients with Hodgkin's disease, malignant melanoma and breast cancer responded to this combination chemotherapy. Objective remissions were obtained also in five of thirteen patients with primary or metastatic brain tumors and in five of nine patients with pulmonary metastases. Nausea and vomiting were the main toxic effects, especially after injections of MNU. Myelosuppression was noted in about 50% of treated patients. Since this combination of cytostatics showed significant antitumor activity, further investigations are necessary on a larger number of patients and in other types of malignant tumors.

Steroidal alkylating agents are supposed to bind to steroid hormone receptors in target tissues. By this interaction the steroid portion might act as a carrier for the alkylating group. Three steroidal agents (phenesterin, estradiol mustard, dehydroepiandrosterone mustard) were tested for their capacity to combine with estrogen and androgen receptors in normal and malignant target tissues. For measuring steroid receptor complexes ager gel electrophoresis was used. All three compounds (added at a 10(3)-fold excess) revealed in vitro no competition to receptor sites (estrogen and androgen binding). After preincubation of intact tissue estrogen mustard was effective in inhibiting the binding of 3H-estradiol and dehydroepiandrosterone mustard reduced the uptake of 3H-5alpha-DHT. This may be due to liberating of estradiol and dehydroepiandrosterone, respectively, from the intact molecule. From these data it is unlikely that the cytostatic steroidal agents are more effective than other alkylating drugs.

The oncogenic effect of ethylnitrosourea (ENU) on rabbits during the organogenesis was studied. ENU, dissolved in sodium phosphate (pH 6.0), was injected in a 50 mg/kg dosis intravenously in pregnant dams between the 8th and 10th day of gestation. From 12 offspring 8 grew up normally and appeared unremarkably until 30--36 months of age when neurologic signs first developed. Six rabbits showed one or more tumors along the peripheral nerves. Two rabbits were bearing brain gliomas in the vicinity of the 3rd ventricle. The tumors of the peripheral nervous system (PNS) were of variable size and soft consistency; they had a cut surface of spongy and even cystic appearance. Histologically, the PNS tumors resemble Schwannomas of the Antoni B type. An ultrastructural study of these neoplasms disclosed cells featuring a basal lamina type of lining characteristics of Schwann cells. These findings demonstrate that the exposure of rabbits to ENU during organogenesis results in the induction of neurogenic tumors which become clinically manifest late in life. It seems, therefore, that the selective oncogenic effect of ENU on the nervous tissues of the exposed animals depends exclusively on the stage of organogenesis at which the drug is brought to bear upon the target organ anlage.