REPORT ON THE APLICATION OF POLAROGRAPHIC EFFECT OF PROTEINS IN CÂNCER DIAGNOSIS

In this report to your society we have not presented our experimental data. We are reserving this more technical aspect for a publication in the near future, and in which due credit is given to the financial support and encouragement, that the Câncer Research Society of Montreal, has given to this research project. By means of the dropping Mercury electrode and by the pepsin, alcohol and sulphosalysilic acid, deproteinisation methods, we have determined the cystine content in various carcinomatic and non carcinomatic samples of blood serum. The maximum high of cystine wave for normal patient serum was 25 mm. and for carcinomatous serum from 35 to 46 mm. The present study, altho only explorating in nature has yielded results of such promise that it is our opinion, the inauguration of a research program on a larger scale is now in order. Polarography may become a new blood test in cancer diagnosis.


REPORT ON THE APLICATION OF POLAROGRAPHIC EFFECT OF PROTEINS IN CÂNCER DIAGNOSIS
Antonio Cantero Instituto de Câncer de Montreal ^)^ITH the aid of a grant asigned by the Câncer Research Society of Mon treal, a study was carried out at the University of Montreal, with the following objectives.
1) To test Bredickas's claim that is possible to differentiate between carcinomatic and non carcinomatic blood sera by means of the dropping mercury electrode (polarography) • 2) To test the possibility of differentiating between normcl and câncer tlssue by means of polarized electrodes.
This study was begun in the fali of 1946, at which time the Câncer Research Society of Montreal put at our disposal a bursary which permitted us to buy the necessary equipment to carry out the first step in our research project.
In 1930, a polarographic effect of proteins was described which consisted of a characteristc wave at the voltage of 1.6 on the current voltage curve of a solution of amonium chloride containing traces of proteins, this efect has been shown to be due to the electrolytic evolution of hydrogen catalysed by the presence of the protein at the cathode interphase.
Since the protein effect has been investigated in the physico-chemical Institute of the Charles University by Dr. R. Bredicka, who introduced a more specific polarographic reaction for the proteins by adding to the) .IN. solution of amoninium chloride and amonia a solution of a coboltous or coboltic salt. he has shown that proteins containing sulphur cause in such Solutions a new wave at a smaller voltage (1.4) and ascribed this effect to the sulphydryl & di-sulphydic groups of the proteins.
In 1936, Purr & Russel found that carcinomatic blood shows in certain biological reaction less activity than nor mal blood.
Waldsmidt & Leitz and his collaborators attempted to use this reaction for câncer diagnosis and expressed the opinion that the lack of activity of the carcinomatic serum is due to decreased activity of the sulphydril groups in the proteins of blood serum.
In our clinicai application we have combined somewhat the Bredicka & Waldsmidt-Leitz methods and have found them both satisfactory in arriving to a diagnosis of blood serum associated with cellular proliferation.
The pathological State indicated by the abnormal height of Bredicka's pro tein wave has been ascertained to be due to carcinoma or sarcoma, if acute caces of infiammation or fever are eliminated.The serum in the latter pa thological State gives with either rea ction an abnormal that is a "positive" effect.Investigations are now being directed towards distinguishing whether the decomposition products of the serum proteins due to câncer are different from those due to other diseases (in fiammation, fever,) so as to make the polarographic reaction in this respect more specific.
At the outset it may be stated that we have been unable to confirm the fool proof diagnostic claims made by Bredicka and Heyrovsky.We feel however that the present sudy has been valuable in an exploratory sense, as it seems to open a promlsing field for further systematic research.
The first systematic research using the polarographic diagnosis of câncer was carried out by Bredicka in collaboration with F. N. Novak, director of radio therapeutie Institute Prague: from 187 cases the polarographic diagnosis agreed in 102 out of 107 histologically ascertained carcinomatous cases, 11 of the 13 sarcoma cases, whilst one the 38 normal sera showed a positive polarographic reaction; of the 29 non carcinomatic diseases, 14 were polarographically positive and 15 negative.II -395 patients attending the butdoor clinics, or were sent to the hos pital for routine laboratory investiga tion or occupied the hospital wards for various ailments.
In the first group, made up exclusively of patients sufering with câncer, the polarographic câncer diagnosis was positive, as to the height of the cystine catalytic wave, and as to the results of the split product waves (Waldsmit Leitz) in 163 cases of câncer.Two ne gative results in one câncer of breast and one câncer of cervix receiving deep X Ray therapy.
In the second group of 395 taken at random in the outdoor or in the hospital wards, there were 13 false positive pola rographic câncer results, in noncancerous patients.But there has been no false negative polarographic câncer diagnosis in those cases wich subsequently have been prove to be carcinomatic sera.
The acute or subacute inflammations, as well as patients receiving high doses of penicilin show a positive po larographic serum reaction.No explanation can be presently advanced as why this should take place.This will be later investigated.
A point which requires further re search is to find out if the polarogra phic serum reaction of câncer patients which have undergone radical surgical, Radium and deep X Ray therapy, show a change in the polarographic effect of the proteins, and which may indicate further presence or complete erradi-cation of the câncer.This part of the research project is now under investigation and the object is to compare the polarographic câncer diagnosis before and after treatment has been considered eficacious.
such promise that it is our opinion, the inauguration of a research program on a larger scale is now in order.Polarography may become a new blood test in câncer diagnosis.
In concluding we wish to call attention to a few of the most important conclusions derivable from the present study.

Conclusion anã Remarks.
In this report to your society we have not presented our experimental data.We are reserving this more technical aspect for a publication in the near future, and in which due credit is given to the financial support and encouragement, that the Câncer Research So ciety of Montreal, has given to this re search project.
By means of the dropping mercury electrode and by the pepsin, alcohol and sulphosalysilic acid, deproteinisation methods, we have determined the cystine content in various carcinomatic and non carcinomatic samples of blood serum.
1) Using Bredicka's procedures and Walchmitz-Leitz procedure, we have been able to substantiate partly the claims of Bredicka and other workers, that the polarograph can be used for the serological diagnosis of câncer.At the present time, the clinicai value of this technique is promising, but has to be proven further.
The manipulation of a polarograph still requires a well trained and well specialized personal.
However, results of both scientific and clinicai importance may be óbtained after further research.
Indications have been obtained that a systematic study of the content of sulphur containing proteins (cystine) in blood cells may yield new Information which is not only of physiological, but also of clinicai importance.
The maximum high of cystine wave for normal patient serum was 25 mm.and for carcinomatous serum from 35 to 46 mm.The present study, altho only explorating in nature has yielded results oí i V ■Vi

A
similar agreement was found in the Finson Institute and Radium Station (Copenhagen) where amongst the positive reactions, some cases of hepatic desorder were ascertained.SINCE 1948, THE POLAROGRA-PHIC CÂNCER DIAGNOSIS IS BEING APPLIED FOR FURTHER CLINICAL investigation & research at the Câncer Institute of Montreal, and where the di rector, Dr. Simard, a member of the Câncer Research Society, Medicai Advisory Board, has given his whole hearted cooperation to the research project.We are herewith including in this report our results of the polarographic câncer diagnosis as applied to cancerous patients at the Câncer Institute of Mon treal.From 1948, to March 1949, blood serum obtained from 560 natients were submitted to polarographic investiga tion.The patients were classified into two distinct groups : I -Patients attending the Tumor Clinic, having received surgical, Radium and X Ray therapy following a positive diagnosis of câncer.This group was made up of 165 patients.