STUDIES ON ENZYME ACTION
XXXI. COMPARATIVE
LIPASE ACTIONSOF HUMANTUMORS
HELEN MILLER NOYES, KANEMATBU SUGIURA,
AND K. GEORGE FALK
From the Ham*man Reeearch Laboratory, The Roosevelt Hospital, and the Huntington
Fund for Cancer Research, Memorial Hospital, New York
INTRODUCTION
.
I t is generally accepted at the present time that enzyme
actions and many of the chemical changes which occur in living
matter and upon which the continuance of the life process
depends are interrelated. In fact, the view is adopted frequently, that many of the necessary chemical changes are
controlled by the enzymes. A systematic study of certain of
the enzyme actions of the Flexner-Jobling rat carcinoma and
of rat, beef, and rabbit tissues, showed definite relations and
regularities in these actions. In the present paper, the lipase
actions of a number of tumors of human origin are presented.
The enzyme content and behavior of various tumor materials
have been studied by a number of investigators. The results
to be presented here treat of the problem in a manner somewhat
different from its treatment heretofore, so that reference to the
summaries and text-books on enzyme actions should suffice 'for
the earlier work.
EXPERIMENTAL METHODS
The experimental methods used, and the reasons therefor,
were described in detail elsewhere.' They will, therefore, only
be outlined briefly here. The tumor, as soon as practicable
after removal, was ground and extracted with a definite quantity
of water overnight in the presence of toluene. The time which
elapsed after the operation until extraction was begun varied
1 K. G. Fslk, H. M. Noyee and K. Sugiura, J. Biol. Chem., 1924,
213, 225.
105
LIX, 183,
106
HELEN M. NOYES, EANEMATSU B U G I U ~AND
,
K. GEORGE FALK
considerably, perhaps between one hour and 24 hours, or even
more in isolated cases. With the latter, the tumor was kept
on ice until used. After extraction, the mixture was filtered
through paper. The filtrates were cloudy or even turbid at
times. They were brought to pH 7.0 with sodium hydroxide
solution and 15 cc. portions tested on equivalent (3.4 milliequivalents) quantities of the different esters for 22 hours at 37".
The enzyme actions were determined by titration with 0.1 N
sodium hydroxide solution with phenolphthalein as indicator.
Toluene was present 'throughout. All determinations were
made in duplicate and the necessary corrections for blanks introduced in every case. The enzyme actions of the solid residues
after the extractions were tested in a number of cases and gave
results similar to those of the extracts. Results are given for
the following esters: phenyl acetate, glyceryl triacetate, methyl
butyrate, benzyl acetate, ethyl acetate, methyl acetate, ethyl
butyrate, methyl benzoate, ethyl benzoate, and isobutyl acetate.
The greater part of the tumor material was obtained from the
Pathological Laboratory of the Roosevelt Hospital through the
cooperation of Drs. W. C. White, G . P. Pennoyer, C. W. Lester,
F. R. Smith, P. Wood, S. H. Thompson, and R. N, Schullinger
of the Staff of the Hospital. A number of tumors were obtained
from Dr. James Ewing and the Pathological Laboratory of
Memorial Hospital, and several from Dr. E. J. Baumann of
Montefiore Hospital. Thanks are due to all of those mentioned
for furnishing the material and for the information with reference
to it upon which this study is based.
The difficulty of obtaining suitable material for an investigation such as this is obvious. A definite type of tumor of
human origin for extended experimental study is only rarely
available. It was necessary to study the material as it came
to hand, with the hope that when a sufficient number of results
had been obtained, regularities would be observed. Fortunately, this hope was fulfilled, and the ester-hydrolyzing actions
permitted of a surprisingly simple grouping for tumors of various
structural or histological types. A question which must be
mentioned here involves the possibility of change in the tumor
BTUDIES ON ENZYME ACTION
107
material between the time of operation and the time of carrying
out the enzyme tests. Such changes may involve bacterial
decomposition, or autolysis, or both. These factors will be
taken up more in detail later.
EXPERIMENTAL REBULTS
Because of the large amount of data, it is impracticable to
give all the experimental results. They have therefore been
grouped as far as possible, and a limited number of experimental
values, which may be taken to be representative, presented in
detail.
Two methods of presenting the lipase or ester-hydrolyzing
actions are used. In the first instance they will be given as the
absolute actions of a certain number of the tumor extracts on
the various esters. Secondly, the results for the actions of any
one tumor extract on a number of esters will be given as relative
actions; that is, denoting the greatest action by 100, and calculating the actions on the remaining esters of that series in terms
of this. It was shown in previous papers that the second method
of presentation is perhaps the more significant, but that for a
satisfactory understanding of the relations, both methods must
be employed.
The results are grouped in a series of tables and charts, a,
table and a chart combined referring to one series of tumors.
They are presented in the following order: Bladder tumors;
lipomas; a number of miscellaneous tumors showing similar
enzyme behaviors; a more extended study of fibromyomas of
the uterus; mixtures of tumor and tissue extracts.
TABLE I
Hydrolyzing Actions in Tenths of Milli-Equivalents of Acid Prodwd by Human
Bladder Tumor Eztracts 012 tha Indicated Esters
108
HELEN M. NOYES, KANEMATSU SUGIURA, AND K. GEORGE FALK
FIG. 1. BUDDERTUMORS,
EXTRACTS.
AVERAGE
OF RAT TUMOR
EXTRACTS
Each curve represents the results with the extract of one tumor. Four of these
tumors were designated as carcinoma of the bladder in the histological findings,
one as cancer of the bladder, and one as papilloma of the bladder. The detailed
findings are not given as they do not, a t present, appear to add to the interpretation
of the results. They are available, however, if desired a t any future time.
The six tumors showed very much the same “pictures” or types of actions.
They are also very much like the FlexnerJobling rat carcinoma type, for which
the average values were taken from the results presented in an earlier paper except
that the results with isobutyl acetate are somewhat smaller with the former. Comparing the absolute actions with the absolute actions found for the corresponding
concentrations with the rat carcinoma actions, the values were found to be somewhat smaller with the human tumor extracts.
TABLE I1
Hydrolgzing Actions in Tenths of Milli-Equivalents of Acid Produced bg Human
Lipoma on the Indicated Esters
LIQUIDS
AND EXTRACTS
FIQ. 2. LIPOMA
The curves for actions of the liquids filtered from two human lipomas after being
ground and the aqueous extracts from the residues after filtration are shown. The
aame types of act.ionsare shown by all; entirely dfferent from that of the FlewerJobling rat carcinoma.
110 HELEN M. NOYES, KANEMATSU SUGIURA, AND K,GEORGE FALK
FIQ.3a. HUMANTUMOR
EXTRACTS.
AVERAQEOF RAT TUMOR
EXTRACTS
TABLE I11
H y d T o & i q Actions in Tenths of Milli-Equivalents o j Acid Produced by a Number
of Human T U ~ OExtracts
T
012 the Indicated Esters
I
Tumor or Tissue
No.
B5b.. . . .
R19.. . . .
B7A.. . . .
68 . . . . . .
R20A1. . .
19.5
38.7
44.4
66.6
88.8
1.11 0.58
2.16 1.31
2.66 1.90
2.93 1.64
4.00 2.78
I
I
0.21
0.64
1.51
0.38
1.23
l
0.11
0.17
0.51
0.16
0.81
0.14
0.24
0.81
0.17
0.57
l
0.13
0.34
1.14
0.34
0.79
l
0.14
0.50
1.44
0.00
0.78
l
0.07 0.04 0.09
0.13
0.62
0.04
0.43
l
0.09 0.17
0.64 0.54
0.02 0.00
0.12 0.68
I
I
STUDIES ON ENZYME ACTION
111
FIQ.3b. HUMANTUMOR
EXTRACTB.
AVERAGEOF RAT TUMOR
EXTRACTS
These curvw, Figs. 3a and 3l1,showing the actions of a number of human tumor
extracts, approach in general the Flewer-Jobling rat carcinoma type and the general
type found with the bladder tumors (Fig. 1). Regularities of a secondary nature,
as illustrated in curves 08 and R44 (teratoid and sarcoma of testicle, reapehtively)
may appear with more data. The histological findings follow:
B5b. Carcinoma of left ovary.
R19. Sarcoma of thigh.
69. Solid alveolar carcinoma of breast.
R20A. Multilocular cyst-adenocarcinoma, papillary.
68. Teratoid of testicle.
B7A. Metastases to liver from Carcinoma of testis or spermatic cord.
B7B. Metastases to spleen from Carcinoma of testis or spermatic cord.
74. Metastases to liver from carcimona of rectum.
R44. Sarcoma of teeticle.
112
HELEN Me NOYES, KANEMATSU SUGIURA, AND K, GEORGE FALK
FIG 4. FIBROMYOMA
OF UTERUSEXTRACTS. TYPEI .
AVERAQEOF RATTUMOR
EXTRACTS
The results shown in Table IV and Fi 4 are strikingly similar to the rat tumor,
as well as to the human tumors shown in%&. 1, 3a and 3b. The histological findings in general were limited to the statements of “Fibromyoma of Uterus.” As
matter of convenience, the actions of these fibroids have been designated “Type I.
:
TABLPJ IV
Hydrolyzing Actions i n Tenths of Milli-Equivalents of Acid P r o d w d bg Extracta
of Fibromyoma of Uterus (Type I ) on the Indicated Esters
STUDIES ON ENZYME ACTION
113
FIO. 5. FIBROMYOMA
OF UTERUSEXTRACTS.
TYPE11.
AVERAGEOF RAT TUMOR
EXTRACTS
The results shown in Table V and Fig. 5 show “pictures” very similar to each
other, b u t entirely different from those of Type I and of the rat tumor and the
human tumors shown in Figs. 1, 3a, and 3b. The histological findings recorded
W e r in no way from those of the fibroids shown in Fig. 4. They were all designated
as Fibromyoma of the Uterus.
The absolute values of these tumor extracts, as shown in Tables I V and V are
considerably smaller than those of the rat tumor and the other human tumors for
corresponding concentrations. A comparison of the Type I and Type I1 Fibroida
with each other is difficult because the pictures are so entirely different.
114 HELEN M. NOYES, XANEMATSUBUGIURA, AND K. GHORGE FALK
TABLHI V
H@rolysdno AdWm in Tentha of Mzui-Eqrcivdenta of Acid producsd bg F i b r r n p n a
of Utemcs (Type 11) Extra& on the Indicated Eatsrs
-
No.
R17B ,..
R16C .. .
87.
RNA
::
RMlA...
Rs.... . .
d
Tumor or Tiague
Extrwted r’cc.
solution
d
&h.
mp.
8.9
36.8
74.4
88.5
88.9
168.7
2.02
1.86
1.66
1.91
0.16
0.38 0.26
0.70 0.47
0.69
1.47
1.10
0.78 0.67
0.63 0.35
It was possible to go farther in the study of these fibroids.
A somewhat more detailed discussion of Types I and I1 is
therefore desirable. The most striking difference in their pictures is in the actions on methyl and ethyl butyrates. For
Type I1 fibroids, the actions are very much greater; in fact, the
actions on the butyrates are, in general, greater than on the
other esters. A second striking difference is shown in the
actions on the last two esters in the plots; for Type I, isobutyl
acetate is greater than ethyl benaoate; for Type I1 isobutyl
acetate is smaller than ethyl bengoate. These two sets of
differences may be taken to be sufficient to characterize the
two types of actions. A number of additional comparisons
might be made which would possibly be useful and, in any event,
are interesting. For example, with the isomers, ethyl butyrate
and isobutyl acetate, the values are greater with the latter for
Type I, and with the former for Type 11; with the isomers
benayl acetate and ethyl benzoate, greater with the former for
Type I, with the latter for Type 11, etc.
In many of the uterine fibroids which were obtained for study,
several distinct tumor masses could be readily separated. I n
the first experiments these separate masses were ground together and extracted aa one unit. Several results of such
treatments gave enayme “pictures” intermediate between
Types I and 11. These results led to a change in the experimental procedure in that with more than one distinct mass
115
STUDIES ON ENZYME ACTION
present in the uterus containing the fibroids, each mass was
tested separately, or where they were small, several of the
smaller masses were combined and tested together. To anticipate the results, it may be stated that in some specimens (each
specimen consisting of uterus plus fibroids), the different
fibroid masses all showed actions similar to Type I, in other
specimens the different fibroid masses all showed actions
similar to Type 11, and in other specimens one or more of the
fibroid masses showed actions similar to Type I and other
fibroid masses in the same specimen showed actions similar to
Type 11.
The experimental results obtained with three of the Mixed
Type fibroids will be presented in Table VI and Figs. 6a, 6b,
and 6c.
TABLE VI
H&d@ng
Actions in Tenths of Milli-Equwaknts of Acid Prduced ba, F i b r o m y m
of Uterus (Mixed type^) Extracts on the Indicded Esters
No.
Tumor or Tiasue
Extrtraoted er 00
Solution Aeeted:
R14Ai.. .
R14B1. . .
181.4
100.8
4.11 2.60 1.26 0.76 0.69 1.03 0.79 0.59 0.20 0.64
1.97 1.39 2.80 0.55 1.23 1.33 2.28 0.73 0.77 0.59
R18A . . .
R18B . . .
R18C . . .
R18D.. .
129.0
123.3
45.8
108.5
(uterine muscle)
104.5
(outer membrane
of uterus)
2.79 1.90 2.75 0.58 1.30 1.41 2.45 0.77 0.77 0.60
Experiment
Rl8E
.. .
...
.. .
R28C . . .
R28D.. .
R28A
R28B
.mg.
88.9
88.9
88.9
88.9
I I I I I I I I I
2.26 1.55 2.47 0.54 1.12 1.23 2.15 0.75 0.72 0.57
1.52
1.33
1.46
0.39
1.07
0.71
1.09
0.11
0.51
1.92
0.42
0.05
0.32
0.27
0.33
0.00
0.25
0.60
0.26
0.04
0.38
0.66
0.37
0.10
0.26
1.59
0.22
0.01
0.12
0.41
0.07
0.01
0.06 0.29
0.37 0.24
0.00 0.33
0.00 -
116
HELEN M. NOYES, KANEMATSU SUGIURA, AND K. GEORGE FALK
FIQ.61%. T W O UTZRINBI FIBROID
EXTRACTS
FROM
Averages of Fibromyoma of Uterus, Types I and 11.
SProCIMEN
R14.
STUDIES ON ENZYME ACTION
117
FIQ.a. THREE
UTERINE
FIBROID
EXTRACTS,
ONEUTERINE
MUSCLE
EXTRACT,
SPECIMEN
R18.
Averages of Fibromyoma of Uterus, Types I and 11.
AND ONE EXTRACTOF OUTER MEMBRANB
OF UTERUS,
FROM
118 HELEN M.
NOPES, KANEMATSU SUGIURA, AND K. QEORGE FALK
EXTRACTS
FROM
FIG.60. FOURUTERINEFIBROID
Averages of Fibromyoma of Uterus,Types I and 11.
SPECIMEN
R28
The following descriptions of the materials extracted for
which the results are presented in Table VI and Figs. 6a, 6b,
and 6c, may be given.
R14A1.-Large central fibroid mass, somewhat colored.
R14B1-Smaller
hard white masses surrounding R14A1.
(Where a tumor mass was too small to give a
complete series of tests several such small maBse8
were combined and tested together.)
STUDIES ON ENZYME ACTION
R18A.-Large
119
hard white fibroid mass, about 49 inches in
diameter.
R18R-Hard mass, about 23 inches in diameter, slightly more
color than R18A.
R18C.-Small hard white masses imbedded in wall of uterus.
R18D.-Uterine muscle with outer membrane of uterus removed.
R18E.-Outer membrane of uterus.
RZ8A.--.Hard, slightly colored; 1 mass 3 inches in diameter
and 6 masses from to 13 inches in diameter.
R28B.-Quite red, slightly greenish and necrotic on border. 1
mass 3 inches and 1mass 13 inches in diameter.
R28C.-In color between R28A and R28B. Two masses, one
2 inches and one 1 inch in diameter.
RBSD.--Decided gray green and brown color with calcified
scales on border.
The three specimens for which the detailed results are presented illustrate the natures of the enzyme actions. They are
not extreme examples or even markedly typical, but represent
merely the average run of the results as they were obtained.
It may be best to give here the number of specimens of uterine
fibroids which were studied and the groups into which they were
divided before discussing the Mixed Type results farther.
Thirty-eight specimens of the fibromyoma of uterus were
studied. Of these, 10 showed Type I actions only; 16 showed
Type I1 actions only; 2 showed Intermediate Type actions;
and 10 showed Mixed Type Actions.
With reference to the histological findings in the Mixed Types,
very little can be said definitely at present. The general report
was " Fibromyoma of Uterus " for all. I n a number of the cases,
sections were taken from the different masses showing different
actions in the same specimen, but here also the findings did not
parallel the enzyme actions except in a few cases. To judge
from the results of Experiment R18 (confirmed by the other
results), Type I1 actions correspond to uterine muscle actions.
With some of the specimens, the masses which gave the Type I
actions were found histologically to correspond to tumor
9
120
HELEN M. NOYES, KANEMATSU SUGIURA, AND K. GEORGE FALK
structures, those which gave the Type I1 actions to correspond
to muscle cell structures, but on the other hand, in some specimens the reverse findings were reported. There was therefore
no parallelism between the types of enzyme actions and the
histological findings even though there is occasional agreement.
The physical properties of the fibroid masses did not give any
indication of the type of enzyme action to be expected and did
not parallel such actions. Such properties included the color,
consistency, and hardness. The question of autolysis or of socalled (‘degeneration” might be raised, but no evidence was
found to show that the different actions were connected with
these, although it is difficult to determine the meaning of these
terms as applied to the material under investigation. The two
types of enzyme action are distinct and cannot be confused
with each other as the few results for which data are quoted
show clearly. The question of bacterial decomposition of the
tumor material may be raised as possibly accounting for the
different types of actions. This was tested in two ways.
Smears were made of material taken from the inner parts of a
number of the fibroid masses which showed the different types
of action. In every case which was tested, the mass was found
to be sterile. The different types of enzyme action were found
therefore with material in which there had been no bacterial
growth before the enzyme tests. Also, a tumor mass was
ground and exposed to the air for a week at the ordinary temperature, thus permitting of large amount of bacterial growth.
The organisms which were identified included Staphylococcus
albus, B . subtilis, B. c02i.l This material was then extracted
with water and the enzyme tests carried out in the usual way.
A comparison of the results of part of the same tumor mass
extracted immediately and tested in the presence of toluene,
gave the same picture for the enzyme actions. The bacterial
growth did not interfere with or destroy the characteristic
enzyme picture of this tumor mass.
The possibility that certain substances are present in tumors
which modify the enzyme behavior of a given tissue so that a
1 Thanks are due Miss Marguerite Fletcher of The Roosevelt Hospital for cafiying
out the bacterial studies in connection with this investigation.
STUDIES ON ENZYME ACTION
121
LIVERMIXTURES
FIQ.7. HUMANTUMOR-RAT
The human tumor was a fibromyoma of uterus, Type I (R28A). The actions
of the mixtures did not differ to any marked extent from the calculated actions
(the sums of the separate actions) except for phenyl acetate where the latter waa
somewhat greater. The types or pictures for the found and calculated actions were
eseentially the same. The objection may be raised that the types of the separate
actions were not very different. This objection is met in the following figures.
common enzyme behavior would be observed with tumors
located in different parts and perhaps showing different structural characteristics, was tested as with the rat and beef tissues,
and rat carcinoma. The reverse assumption, that the possible
presence of certain substances peculiar to a given tissue might
conceivably modify an enzyme behavior common to all tissues
is a different statement of the same underlying thought. The
122
HELEN M. NOYES, KANEMATSU SUGIURA, AND K. GEORGE FALK
FIG.8. HUMAN
TUMOR-BE~F
KIDNEYMIXTURE~S
The human tumor was a fibromyoma of uterus, Type I (R31). The boiled
extracts showed no actions alone. The boiled kidney extract did not influenoe the
tumor actions, but the boiled tumor extracts increased the absolute kidney actions
somewhat, but without changing the type. The actions of the mixtures as found
were smaller for phenyl acetate and glyceryl triacetate than the calculated actions
(sums of the separate actions) but practically identical for the other esters. The
types were essentially the =me for the found and calculated results; B striking fact
in view of the difference in type of the individual actions. It may he pointed out
that the absolute actions in this series are small and thus make possible a magnification of any experimental errors which may have occurred.
possibility outlined can be readily tested by studying mixtures
of tissue and tumor extracts. A number of such experiments
with tissue and rat tumor extracts have already been described.
STUDIES ON ENZYMB ACTION
123
FIG.9. HUMANTUMOR-BEEF
LUNGMIXTURES
The human tumor was the eame as that shown in Fig. 8 (Fibromyoma of Uterus,
Type I (R31)). The conclusions to be drawn from this experiment are the same
as those drawn from the experiment pictured in Fig. 8. The Merent type or picture
of the beef lung actions as compared with the beef kidney and human tumor, is
oflinterest, in view of the identity of the conclusions pointing to an arithmetical
summation of the separate actions in the mixtures.
In order to make the.study of human tumors more complete,
the results of a number of similar tests in which human tumor
extracts were used will now be given.
124
HELEN M. NOYEB, KANEMATSU SUQIURA, AND K. GEORGEFALK
The experimental method was the same as before except that
in the tumor-tissue mixtures, 5 cc. of each extract were used and
5 cc. of water added to make up the usual 15 cc., and in preparing the boiled extracts, these were boiled over a free flame
FIQ. 10. HUMANTUMOR-BEEF
KIDNEY
MIXTURES
for 5 minutes, made up to original volume, and then 5 cc.
portions diluted to 15 cc. with water, or mixed with 5 cc. of
unboiled extract, 5 cc, of water added and tested in the usual
way. Results will be given for mixtures of extracts of human
tumors with extracts of beef lung, liver, and kidney, and rat
liver.
STUDIES ON ENZYME ACTION
125
TUMOR-BEEF
LIVERMIXTURES
FIQ. 11. HUMAN
The human tumor in these two experiments (Figs. 10 and 11) was the same, a fibromyoma of the uterus, Type I1 (R22). Similar conclusions may be drawn from the results of the two experiments. The boiled extracts, kidney, liver, or tumor, had no influence on the actions of the unboiled extracts. The calculated values for the
mixtures were greater than the found actions; but the types or pictures of the calculated
and found actions were essentially the same. This would appear more clearly if percentage actions had been plotted in place of absolute actions. There are apparently
amall variations with isolated esters, but these are not marked enough to warrant definite conclusions or exceptions to the above statements a t the present time.
The results are given in five figures (Figures 7 to 11) and are
plotted as absolute actions (tenths of milli-equivalents of esters
hydrolyzed). The concentrations of tissue and tumor extracted
126
HELEN M. NOYES, KANEMATBU BUGIURA, AND K. GEORGE FALK
when stated as c = 1 signifies 8.9 mg. of each per cc. of final
solution tested; other concentrations are given as multiples
of this.
I n the figures, the ordinates show amounts of hydrolysis in
tenths of milli-equivalents of acid formed from equivalent
amounts of the indicated esters which are plotted at equidistant
intervals on the abscissa axis.
The general conclusion to be drawn from the results of the
experiments with mixtures is that the types are additive and
that there is no specific influence of a tissue or tumor extract
which may change or modify the characteristic picture of a
tumor or tissue. The absolute actions ‘of the mixtures are
frequently less than the sums of the separate actions as given.
As stated in a previous paper, and shown experimentally in
one case, these differences may be referred mainly to the fact
that the enzyme action of a given material in the case of a
number of those studied was not proportional to its concentration. Consequently it is not surprising that the action of a
mixture containing two materials each of a definite concentration is less than the actions of the materials alone each of
the same concentration as in the mixture.
I n the mixture experiments as given, it will be noticed that
the human tumor material used consisted only of the two types
of fibromyomas of the uterus. This was due to the fact that
only with these tumors was sufficient material available to
make possible complete series of tests. While this may apparently introduce an element of incompleteness in the experiments and therefore in the conclusions, the results are sufficiently
clear cut and definite, especially when taken in connection
with the results on the tissue mixtures and rat tumor-tissue
mixtures previously reported, to justify the conclusions stated:
that the ester-hydrolyzing actions are additive and with each
tumor or tissue the actions are found to be peculiar to the
tumor or tissue, and independent of certain substances, distinct
from the enzyme.
The protease actions of a number of the human tumor
extracts were determined in a manner similar to the lipase
STUDIES ON ENZYME ACTION
127
tests with definite quantities of peptone, casein, and gelatin
as substrates for 22 hours at 37”. The formol titration method
was used. The results obtained did not show any striking or
regular differences in the actions of the various types of tumors.
The absolute actions were large enough to show that definite
proteolytic enzymes were present, especially with peptone and
casein, the actions on the gelatin being much smaller as a rule and
frequently of negligible magnitude. The lack of systematic
differences in the actions of the different tumors may be ascribed
in great part t o the lack of definiteness in the chemical change
studied. A total action was measured in each case, and while
it is not only conceivable but probable that different peptide or
other groupings are hydrolyzed in the protein molecule by
different tissue or tumor enzyme preparations, these distinctions
would not appear in the results obtained. Certain rough
generalizations in connection with the total actions might appear
as with the rat tissues, but they are even less marked in the
present instance, and do not add to the results on the esterhydrolyzing actions already given.
DISCUSBION OF RESULTS
Certain facts stand out, clearly in the experiments described.
A number of bladder tumors and other tumors of various types
gave similar “pictures ” for their comparative lipase actions.
These pictures were essentially the same as those obtained with
the Flexner-Jobling rat carcinoma. Fibromyomas of the uterus
were found to fall definitely and distinctly into two groups; one
showing pictures similar to the rat carcinoma and the human tumors just mentioned, and one similar to the picture given by the
uterine muscle. The rat carcinoma picture is therefore not characteristic of tumors generally termed malignant, since there was
no evidence of malignancy as ordinarily understood, with the one
group of fibromyomas. Furthermore, both types of actions
occurred with different masses in the same uterus containing a
number of fibroids. It is of interest to note, however, that the
pictures obtained with the non-malignant lipomas were entirely
distinct from the rat carcinoma picture.
128
HELEN M. NOYES, KANEMATSU SUQIURA, AND K. QEORQE FALK
The relation of these enzyme actions to the histological
findings is of interest. In the first place, essentially the same
picture was found for the enzyme actions of a number of tumors
where the histological results showed great differences in the
characters of the tumors. I n the second place, the pictures of
the enzyme actions of a number of fibroid masses were unquestionably different in cases where the histological findings
were essentially the same, or did not parallel these differences.
These differences between the enzyme actions as found by the
chemist, and the histological structures as determined by the
pathologist are, at first sight, extremely disturbing. If it be
considered, however, that two different phenomena are under
investigation, in the one case a function of a given material,
in the other case its structure, it may become clear that there
are not, necessarily, contradictions involved in the two sets of
results. Further studies may bring out relationships of significance between the functional and structural properties of
the materials.
The writers wish to thank Dr. E. B. Sanford, of The Roosevelt
Hospital, for his advice and aid in various phases of this investigation. Thanks are also due Mr. Isaac Lorberblatt for his
assistance in carrying out the experimental work described in
this paper.
SUMMARY
The lipase or ester-hydrolyzing actions of a number of tumors
of human origin were tested on ten esters. The results are
presented as “pictures” of the relative actions on the different
esters and as absolute actions. The “pictures” of the relative
actions show a definite grouping for the different tumors; the
“pictures” of one group of actions being similar to the “picture”
of the actions of the Flexner-Jobling rat carcinoma, those of a
second group entirely different. The classifications do not
correspond in general to the classifications based upon the
histological findings. The possible significance of the experimental results is discussed.