In an earlier, detailed study of 92 patients suffering
from malignant disease and all receiving cytotoxic drugs,a number
of interesting facts emerged.
Of these, two were considered of particular interest.
It was noted that in 60%, of the total cases the α-2-globulin
fraction of the serum electrophoretic pattern was raised, often
to a considerable degree. If the cases of locally advanced
disease or those demonstrating metastases were alone considered,
then the percentage showing a raised α-2-globulin fraction was 76.
Secondly, it was found that the serum and urinary uric acid levels
were frequently raised in malignant disease and could be further
altered by treatment with cytotoxic drugs or radiotherapy.
During this original study I further became impressed by the
lack of an objective means of determining tumour response to
cytotoxins (or radiotherapy) at an early stage in the treatment.
The significance of these changes in the protein pattern and
in the uric acid levels in plasma and urine is obscure and
relatively scant attention has been given to these problems in
It was known that changes occur in the globulin fraction
of the plasma proteins in certain liver diseases. Gelhorn,
in 1958, reported a greater agglutination of leucocytes of
cancer patients than of those of normal patients by an antiserum
prepared against the α-2 fraction of the serum No report,
however, was made of the actual levels of α-2-globulin found in
the serum of these patients.
In 37 cases of metastatic carcinomatosis Sunderman (1964)
demonstrated a significant increase in the mean concentrations
of α-1 and α-2 globulins in the electrophoretic fractions of
the serum proteins He was of the opinion that these increases
constituted a common and non -specific pattern which should not
be regarded as evidence of neoplastic disease. No attempt was
made to determine the significance of these findings, but the
comment was made that these changes "might be of value in
Although a slightly different problem, it is of interest
to note that Macbeth and his co- workers in Edmonton were able to
demonstrate an elevation of the carbohydrate fraction of the
plasma glycoproteins in patients and experimental animals
harbouring malignant neoplasms. They commented that this
elevation was not specific for malignant disease but was intimately
related to the neoplastic process. They further drew attention
to the lack of information concerning the significance of these
It thus appears that, although a very considerable amount of
work is in progress on such problems as the ultrastructure of
malignant cells, the various aspects of nucleic acid synthesis
and metabolism, and on the problem of immunity in malignancy,
relatively little work has been done, at a clinical level, on the
significance and potential value of the changing patterns of
α-2-globulin in malignant disease.
Even less information is available on the changes which
occur in uric acid levels in plasma and urine in malignancy,
particularly after treatment with cytotoxic drugs. It was known
that hyperuricaemia could be produced by radiotherapy, steroids,
or cytotoxic drugs in leukaemia and reticulosis, and that on
occasion hyperuricaemia may be sufficiently severe to cause acute
renal failure: The employment of serial uric acid determinations
in plasma and urine as a means of assessing response to cytotoxic
treatment of solid tumours has, however, not been reported.
It was therefore considered that by a detailed study of the
changes in serum electrophoretic pattern, with particular reference
to the α-2-globulin fraction, together with a simultaneous study of
the changes in plasma and urinary uric acid levels before and after
treatment with cytotoxic drugs, some diagnostic and prognostic
significance might derive from the results obtained.