Increased incidence of lung metastases of sarcoma 276 bearing XVII/Berlin mice after total body irradiation and BCG.

Combined prophylactic treatment by total body irradiation and BCG produce an increase in lung metastasis incidence and pleural effusions in a syngeneic murine tumor model. The prophylactic effect of BCG on metastasis formation is abolished independently of the order of pretreatments. Several possible causative mechanisms underlying this phenomenon and the clinical implications are discussed.

Inhibition of hematogenous metastatic dissemination by BCG-stimulated serum obtained from rabbits and mice.

A statistically significant metastasis-prophylactic effect was obtained by administration of sera originating from BCG-stimulated mice and rabbits. The benzo[a]pyrene induced sarcoma 276A served as experimental metastatic test model.

Effectivity of living and non-living BCG vaccine on experimental metastatic spread in mice and the stimulation of the reticulohistiocytic system (RHS).

Heat-killed or formalin-killed BCG vaccine caused statistically significant increases in weight of lungs, spleen and liver, which were in the same range as after administration of equal doses of viable BCG vaccine. Similarly, there was no quantitative or temporal difference in the phosphatase-positive proliferations of the RHS in liver spleen and lungs when using identical doses of viable or heat- or formalin-killed BCG vaccines. The metastasis-prophylactic effect demonstrated for viable BCG was present also after administration of the killed vaccines to a statistically significant degree. The increases in organ weight, extent of phosphatase-positive proliferation foci in liver, spleen and lungs as well as the metastasis-prophylactic effect were entirely identical; they seem to be in a close relationship with each other.

Experiments to increase the selectivity of tumor chemotherapy by means of in vivo activation of transport forms of cancerostatics by exogenous enzymes.

A significant tumor damaging effect (growth inhibition) on transplanted syngeneic sarcoma in mouse was obtained by means of pH-dependent activation of a transport form of a cancerostatic drug by an enzyme foreign to the organism. This effect was achieved by combined administration of 8-0-(alpha-L-arabinofuranosyl)beta-peltatin-A as a transport form of beta-peltatin-A and the exogenous enzyme alpha-L-arabinofuranosidase from Aspergillus niger and additional increase of the acidity of the tumor by injection of glucose. The combined application of the transport form plus enzyme showed a more favorable effect on selectivity than free peltatin when a quantitative comparison was made between the tumor growth inhibition and the damage to the blood picture.

[Selective, time dependent accumulation of the triphenylmethane dyes bromphenol blue, bromoresol green and iodophenol blue in mouse tumors]. / Uber eine selektive, zeitabhängige Anreicherung der Triphenylmethanfarbstoffe Bromphenolblau, Bromkresolgrün und Jodphenolblau in Mäusetumoren.

1. A selective late dye concentration dependent on the time is described for 3 triphenylmethane dyes namely bromphenol blue, bromcresol green and iodophenol blue after intravenous application in high dosage in malignant inoculated tumors and experimental tumor metastases in the mouse. 2. The possible mechanisms of this dye concentration phenomenon in the tumor tissue as well as some chances of the eventual therapeutic and tumor diagnostic utilization were discussed.

[Cleavage of alpha-L-arabinofuranoside, beta-D-glucopyranoside and beta-cellobioside of 4-nitrophenol by enzymes of various fungi - a contribution to increase the selectivity of tumor therapy]. / Spaltung des alpha-L-Arabinofuranosids, beta-D-Glucopyranosids und beta-Cellobiosids von 4-Nitrophenol durch Enzyme verschiedener Pilze--ein Beitrag in Verbindung mit Versuchen zur Steigerung der Selektivität der Tumortherapie

To carry out long-term experiments as part of a therapy concept of malignant tumours using inactive transport forms of cancerostatic substances and their specific cleavage in the acidic pH region of the tumours by application of extraneous enzymes, we require enzymes with similar catalytic and pharmacokinetic properties which differ from each other in immunological respect. In the search for such enzymes, the alpha-L-arabinofuranosidases from 12 different fungi, among them 9 basidiomycetes, were studied. The enzymes mentioned were demonstrable in all fungi. Optimum pH values ranged between 2.5 and 5.5. The Km values for the cleavage of alpha-L-arabinofuranoside were, in most cases, 0.5 to 1.8 moles-liter-1-10(-3). With regard to pH dependence, the alpha-L-arabinofuranosidases of most of the fungi investigated proved adequate for the long-term trials envisaged. 4-nitrophenyl-beta-D-glucopyranoside and -beta-cellobioside were also cleaved by enzyme preparations of all the 11 fungi investigated. The beta-D-glucopyranosidases showed a less favourable pH dependence than the alpha-L-arabinofuranosidases. The cleavage of 4-nitrophenyl-beta-cellobioside, on the contrary, showed mostly a comparatively favourable pH dependence. On the basis of the coinciding optimal pH values and the occurrence of 4-nitrophenyl-beta-D-glucopyranoside as an intermediate product in the cleavage of the corresponding cellobioside, we assume that both substrates are cleaved by beta-glucosidase. Because the occurrence of the glucoside during the cleavage of cellobioside is undesirable for the therapeutic trial, a method is proposed for selection of an appropriate cellobioside splitting enzyme basing on the present studies and the relevant literature.

Temperature dependent pH-instability of some alpha-L-arabinofuranosidases.

In this paper are described alpha-L-arabinofuranosidases, partially purified from some moulds, with very high lability of their activity to weakly alkaline or neutral pH-values. This pH-lability strongly depends on temperature. The form of the inactivation curves suggests involvement of charge changes in this irreversible process. These enzymes may be useful for optimization of the tumor therapy concept described by Graffi (5).

Inhibition of experimental metastatic spread by nonspecific stimulants.

It has been demonstrated by a syngeneic metastatic model of the XVII mouse that pretreatment of the animals with BCG and Freund's adjuvant brings about a significant inhibition of metastatic growth. This inhibition is further increased by combined pretreatment with nonspecific stimulants and additional specific immunisation of the animals against the given tumor.

[Mesothelioma in syrian hamster. V. Macroscopic and histologic investigation of transplanted mesothelioma in solid and ascitic form (author's transl)]. / Mesotheliome beim Goldhamster. V. Makroskopische und histologische Untersuchungen an transplantablen Mesotheliomen in solider und Aszitesform

Transplantable mesothelioma lines are described, which have been inoculated successively either s.c. or i.p. in solid and ascitic form. Increases of the degree of malignancy could be demonstrated for macroscopically biological parameters. The latent periods became shorter with increasing in vivo passages. In the histological picture, progressive dedifferentiation of the tumour cells with rising tendency towards infiltrative growth was observed.