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.

Foamy virus Type II persists in the haematopoetic organs of 75 percent of baboons in the Suchumi flock. A mixed infection with foamy virus types I and II seems to be possible. Foamy viruses are isolated as well from monkeys with haemoblastoses as from healthy animals. New information concerning the intrauterine transmission of foamy viruses were obtained.

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.

1. Application of hamster papova virus to newborns of Syrian hamster has produced some s.c. sarcomas after a 5 to 6 month latency period, by virtue of the strong inducer effect of this papova virus to endogenous (latent) oncorna viruses. 2. Cellfree filtrates from a polymorphorus-cell sarcoma produced in this way, when applied to newborn hamsters of the spontaneously tumour-free hamster line HaP, again lead to sarcoma formation after a latency period of 3--8 months in about 20% of the animals; the same holds for cellfree filtrates of these cellfree induced sarcomas and their transplantation generations. 3. In these tumours C-type oncorna viruses, but no papova virus, could be demonstrated regularly. 4. The hamster specificity of this sarcoma virus is suggested by the complete absence of a tumorigenic effect of the cellfree filtrates from these hamster sarcomas in mice and rats. The preferential induction of hamster sarcomas by sarcoma filtrates, in conjunction with the fact that filtrates from hamster leukoses, indicates a certain difference between hamster leukemia and hamster sarcoma viruses.

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.

Morphological studies on sarcomas induced in syrian hamsters by cellfree transmission are described. The tumour tissue for the cellfree preparations stemmed from a sarcoma, containing C-particles. Basically, three histological groups have been distinguished: 1. neoplasms of the peripheral nerve-sheath, 2. undifferentiated sarcomas, and 3. liposarcomas. Furthermore, a rhabdomyosarcoma, an angiosarcoma and, in a heterotransfection on rat, an osteosarcoma have been established. The great majority of tumours could be transmitted by cellfree preparations. To this neoplasms belong the undifferentiated histological structure.

The efficiency of different intravenously-given BCG doses on the RHS was investigated in the present paper. A time- and dose-dependent increase in the weight of liver, spleen, and lungs, was demonstrated in BCG-treated animals. It was shown, by means of histochemical methods, that the weight increase is due to an enhanced proliferation of cells with acid phosphatase reaction. There is a good correlation between the results obtained with biometric and histochemical methods. The question as to whether there is a direct connection between the proliferation of phosphatase-positive cells of the RHS and an increase in tumour defense especially in the model of metastasizing is under discussion.

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.

A virus of the paramyxo-type was eliminated from cell-free material of human oncornavirus-producing cell lines (PMF). After transmission of this paramyxovirus-free inoculum to a human permanent cell strain (Tu 197/Tr 1) oncornaviruses were permanently formed and no paramyxoviruses could be detected. The paramyxovirus-free, oncornavirus-producing PMF-39 cell line could be established after inoculation of the TU 197/Tr 1 line with cell-free material containing both oncorna- and paramyxovirus diluted 1 to 1000. A second way of elimination of the paramyxovirus was the treatment of cell-free material containing both viruses with antisera against paramyxovirus. In the Tu 197/Tr 1 line inoculated with such material only oncornaviruses were formed. The second paramyxovirus-free oncornavirus-producing cell line was designated PMF 50.

Immunodiffusion analysis of the PMF virus which was detected in malignant permanent human cell lines revealed positive reactions with antisera against the Mason-Pfizer monkey virus (MPMV). No cross-reactivity was demonstrated with murine leukemia virus (MuLV), rat leukemia virus (RaLV), hamster leukemia virus (HaLV), feline leukemia virus (FeLV), simian (woolly monkey) sarcoma virus (SSV-1) and mouse mammary tumor virus (MTV). The cross-reactive antigens of the PMF virus and the MPMV are considered as evidence for the human origin of the PMF virus.

Immunodiffusion analysis of the PMF virus which was detected in malignant permanent human cell lines revealed positive reactions with antisera against the Mason-Pfizer monkey virus (MPMV). No cross-reactivity was demonstrated with murine leukemia virus (MuLV), rat leukemia virus (RaLV), hamster leukemia virus (HaLV), feline leukemia virus (FeLV), simian (woolly monkey) sarcoma virus (SSV-1) and mouse mammary tumor virus (MTV). The cross-reactive antigens of the PMF virus and the MPMV are considered as evidence for the human origin of the PMF virus.

AbstractDurch Reaktion von Tetra‐O‐acetyl‐L‐arabinose bzw. 1, 2, 3, 4‐Tetra‐O‐acetyl‐β‐D‐xylose sowie Octa‐O‐acetyl‐β‐cellobiose mit 4‐[N, N‐Bis‐(2‐chloräthyl)‐amino]‐phenol · HCl entsprechend dem HELFERICH‐Verfahren und anschließende ZEMPLÉN‐Entacetylierung werden die Glykoside 1f, 2b und 3 b erhalten, in denen die alkylierende Aktivität der N‐Lost‐Gruppierung herabgesetzt ist. Über die pH‐abhängige Spaltung dieser Glykoside und ein daraus resultierendes Therapie‐Konzept wird kurz berichtet.

Folgende Grunde und Gesichtspunkte rechtfertigen gerade auch im Hinblick auf den eigentlichen Zweck der experimentellen Krebsforschung, namlich der Krebsbekämpfung beim Menschen zu dienen, eine ausfuhrlichere Darlegung der murinen Leukamien und der sie verursachenden (onkogenen) Viren:

A melanin containing skin tumour of trichoepitheliomatic character, induced by a virus some 40 nm large, is described showing neither infiltrative nor metastasizing growth. The multiple, flat, mostly confluent tumour nodes appear in all parts of the skin, especially in dorsal skin, at the chin, eyes, and ears. The tumours are mostly blue black as a result of hemosiderin and melanin deposits; these pigmentations occur in connective-tissue cells, the tumour cells and the abounding keratinizing cysts. The blastomic character of these tumours, which in part are reminiscent of tricho-epitheliomas, can be demonstrated by transplantation experiments, in which with increasing number of passages are observed a decrease of latent period, disappearance of pigment formation, and increase in histologic de-differentiation.