154
F. Ε.
LEHMANN
In both these cases there arises the question as to what are the
biological factors involved in a selective inhibition of growth. In
regeneration as well as in tumours an intense proliferation of cells seems
to be characteristic. The increase in proteins and in nucleic acids,
especially in the cytoplasm, seems, according to recent results to be the
primary precursor of growth, whereas the increase in cell number by
mitosis appears only as the consequence of the augmented protein and
nucleic acid content of the cells.
From this viewpoint the application of antimitotic substances to
growing tissue appears rather questionable because the primary
processes of increasing cytoplasmic material need not necessarily be
influenced by special inhibitors of mitosis. But at present the action of
mitotic inhibitors must be discussed since numerous authors have tried
to inhibit tumour growth by means of them.
Our research group for developmental and tumour biology has taken
this situation into consideration in planning its experimental procedure.
First we wanted to show that inhibition of growth in regenerates and
tumours can be brought about by the synergistic effects of different
morphostatic substances which are not necessarily antimitotics. In some
cases it can be demonstrated that tissue-specific proteases (cathepsins)
are involved in growth and regression of tissues. Furthermore it has
been possible to influence considerably the activity of cathepsins by
certain morphostatic substances. This leads to the experimental possibility of stimulating cathepsins by chemical factors in regenerates and
of bringing about tissue regression by their activation.
II. Combined Action of Several Inhibitory Substances
and the Total Suppression of Growth
The suppression of the growth processes, selectively by chemical
agents has been proposed in medical tumour research and adopted as an
aim of developmental biology. As can be seen from Loustalot's review
(1957), in experimental chemotherapy of malignant tumours attempts
have been made to synthesize substances which suppress cell division
and which induce subsequent death, regression and resorption of the
cell masses of the tumour. Such cytostatic substances have been discovered by several authors by trial and error. But discoveries of single
substances which induce in experimental animals, total tumour regression with certainty in all cases (Oettel and Wilhelm, 1957; Domagk,
1956; Druckrey et ah, 1958) have remained rather scarce in spite of
the enormous number of investigations involved. Although the direct
attack on malignant tumours by antimitotic substances has not been
too successful from a practical viewpoint, it has furnished nevertheless
F. Ε.
LEHMANN
In both these cases there arises the question as to what are the
biological factors involved in a selective inhibition of growth. In
regeneration as well as in tumours an intense proliferation of cells seems
to be characteristic. The increase in proteins and in nucleic acids,
especially in the cytoplasm, seems, according to recent results to be the
primary precursor of growth, whereas the increase in cell number by
mitosis appears only as the consequence of the augmented protein and
nucleic acid content of the cells.
From this viewpoint the application of antimitotic substances to
growing tissue appears rather questionable because the primary
processes of increasing cytoplasmic material need not necessarily be
influenced by special inhibitors of mitosis. But at present the action of
mitotic inhibitors must be discussed since numerous authors have tried
to inhibit tumour growth by means of them.
Our research group for developmental and tumour biology has taken
this situation into consideration in planning its experimental procedure.
First we wanted to show that inhibition of growth in regenerates and
tumours can be brought about by the synergistic effects of different
morphostatic substances which are not necessarily antimitotics. In some
cases it can be demonstrated that tissue-specific proteases (cathepsins)
are involved in growth and regression of tissues. Furthermore it has
been possible to influence considerably the activity of cathepsins by
certain morphostatic substances. This leads to the experimental possibility of stimulating cathepsins by chemical factors in regenerates and
of bringing about tissue regression by their activation.
II. Combined Action of Several Inhibitory Substances
and the Total Suppression of Growth
The suppression of the growth processes, selectively by chemical
agents has been proposed in medical tumour research and adopted as an
aim of developmental biology. As can be seen from Loustalot's review
(1957), in experimental chemotherapy of malignant tumours attempts
have been made to synthesize substances which suppress cell division
and which induce subsequent death, regression and resorption of the
cell masses of the tumour. Such cytostatic substances have been discovered by several authors by trial and error. But discoveries of single
substances which induce in experimental animals, total tumour regression with certainty in all cases (Oettel and Wilhelm, 1957; Domagk,
1956; Druckrey et ah, 1958) have remained rather scarce in spite of
the enormous number of investigations involved. Although the direct
attack on malignant tumours by antimitotic substances has not been
too successful from a practical viewpoint, it has furnished nevertheless