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The influence of age of experimental animals on the antileukemic activity, toxicity and distribution of ambazone, a new potential antineoplastic agent, was studied in 2- and 12-month-old B6D2F1 mice. The predominant effect observed was a significant reduction of the antileukemic action of this compound in old-aged mice. Together with a slight increase in several toxicity parameters this caused a marked reduction of the therapeutic index in 12-month-old mice compared to younger individuals. Furthermore, a general tendency to increased ambazone levels in liver, kidneys and thymus of old-aged mice was observed. Our data therefore provide further evidence that age has to be taken into consideration as one factor that may account for the variety of drug response frequently observed during clinical therapy with anticancer agents.

Conventional X-ray methods and ultrasound tomography are the general basic imaging modalities in oncology. These methods are important for tumor detection as well as for further diagnostic decision making. In the diagnosis of thoracic and bone tumors the conventional X-ray methods still are of high diagnostic value. CT and MRI are complementary methods for extension diagnosis. In the diagnostics of gastrointestinal tumors the complementary endoscopic-radiologic examinations are the initial procedures. Tumors of the liver, pancreas and bile ducts require the application of ultrasound tomography and US-guided fine needle biopsy. In these cases CT provides additional information. Tumors of the kidney can be detected by sonography. Primary diagnostic methods in tumors of the urinary bladder are the cystoscopy, delayed cystography and sonography. CT and MRI are the predominant procedures in the diagnosis of brain and spinal cord tumors. Conventional X-ray methods represent the basic imaging procedures, and, combined with digital radiography, conclusive ultrasound tomography a necessary part of the complex tumor diagnosis.

We have developed a novel and efficient transfection method based on the introduction of foreign DNA into mammalian cells in form of complexes of vector DNA with the nuclear protein HMG1. In this study, it is shown that a stabilization of the complexes against dilution dissociation by addition of soluble CaCl2 or by excessive HMG1 enhances the transfection efficiency. Furthermore, there are no differences in the transfection abilities between the 3 topological DNA forms, viz., supercoiled, open relaxed and linear DNA, if delivered to cells as HMG1-DNA complexes. It is further shown that transfection-inactive complexes of the core histones with foreign DNA can be activated in transfection by the addition of HMG1.

Changes of the sialic acid content of patients sera reflect growth processes of benign and malignant character. Using an enzymatic test the value of sialic acid as a primary diagnostic parameter has been investigated. We found a poor diagnostic sensitivity with exception of lung and ovarian carcinomas where the sensitivity attained nearly 90%. In monitoring of patients with pre-therapeutically elevated sialic acid content in serum dropping values indicate a successful therapeutic intervention. An increase of post-therapeutic values demonstrates recurrent processes but the reaction of the serum level may be delayed up to 2 weeks. The outcome of the studies supports the notion that sialic acid is a tumor marker of very limited value.

Dietary influences on carcinogenesis have been shown in various tissues on the basis of epidemiological and experimental approaches. The present paper demonstrates that the oral application of fructose over long periods to rats previously treated with N-nitrosomorpholine increases the incidence of atypical acinar cell nodules (AACN) in the pancreas. Whereas an increase in AACN was statistically significant (P less than 0.005), no effect on ductule-like structures was detectable. AACN have been regarded as precursor lesions of the acinar cell carcinoma. Although the AACN observed frequently exhibited severe atypia and numerous mitotic figures, no clearcut evidence for malignancy could be detected under our experimental conditions.

Bovine leukemia virus (BLV) was inoculated into one-day-old chickens. In a small part of inoculated chickens leukemia developed during observation period of one year. Out of 88 birds inoculated, only 4 developed histopathologically verified leukemia. The induced leukemia was characterized by enlarged liver and spleen. The organs were infiltrated with leukemic cells. The DNAs of body organs of inoculated chickens were analysed by Southern blot hybridization for the presence of BLV specific sequences. Out of 9 suspicious chickens tested in 6 birds the BLV was found to be integrated into host DNA either as a complete viral genome or as a part corresponding to its 3'-end. The leukemic cells were monoclonal as regard to the integration site of the BLV provirus. Neither the expression of BLV provirus in chicken leukemic cells nor the antibody response to BLV antigens in inoculated birds was detected. The rearrangements and amplification of erb-B and myb loci of protooncogenes in leukemic cells was detected. There were no changes in loci of following protooncogenes: myc, sis, fes, fps, erb A, src and yes. All obtained data taken together suggest that the BLV induced leukemia in chickens is caused by insertional mutagenesis.

Outpatients with inoperable far advanced hepato-cellular carcinomas (n = 5) were treated with LDCY--300 mg/m2 i.v. every 28 days-, echinacin--60 mg/m2 i.m.--and thymostimulin--30 mg/m2 i.m., day 3-10 after LDCY, then twice a week. Therapy was well tolerated by all patients. Their Karnofsky' index increased for 10% in the mean. A stable disease for more than 8 weeks was documented by abdominal ultrasonography in one patient. Serum levels of Alpha-Fetoprotein (AFP), Carcinoembryonic Antigen (CEA) and Tissue Polypeptide Antigen (TPA) did not increase in 2 patients. Median survival time was 2.5 months. One patient is still alive after 8 months. Absolute numbers of CD8+ cells significantly (p less than 0.02) decreased for 7% 1 day after LDCY, whereas CD4+ cells increased (p less than 0.02) from day 1-7. Numbers of natural killer (NK-) cells increased for 17% (p less than 0.05), their activity for 90% (p less than 0.05). Activities of peripheral polymorphs (p less than 0.05) increased for 27% and of Lymphokine Activated Killer (LAK-) cells for 180% (p less than 0.05).

On rats hypothermia of 22 to 20 degrees C and rewarming to normal body temperature leads to an amplification of the hyperglycemic tumor acidification. Mechanism and significance of this effect are discussed.