Cancer chemo(toxico)therapy revisited and alternative ways of healing.A thesis presented to the Anglo-American Institute of Drugless Therapy and leading to the Degree of Doctor of Naturopathy (N.D.).
© 1990 by Dr. Henri Rosenberg.
Introduction 2
Chapter I : Chemo(toxico)therapy 3
Chapter II : Amygdalin - Vitamin B 99
Chapter III : The Synthetic Physiatrons 128
Chapter IV : Trypanosoma Therapy 140
Chapter V : Selenium Therapy 146
Chapter VI : The beer's yeast cure 156
Chapter VII : Tumor related indicators 164
Chapter VIII : The Thymus Therapy 188
Chapter IX : The H-11 Therapy 194
Chapter X : Antineoplaston 202
Chapter XI : Gelum Oral RD® 205
Chapter XII : Neoblastine® 212
Chapter XIII : The WIEDERMANN cure 219
Chapter XIV : Beetroot (juice) as cancer therapy 225
Chapter XV : Integral Fasting Therapy 229
Chapter XVI : The Iron Cancer Cure 235
Tumor related indicators
BackgroundRight up to the sixties it was generally accepted that cancer cells develop from normal healthy cells, the genetic potential of which is differentiated in varying degrees according to tumor type.
For this reason no search was made for possible standard tumor indicators which would only occur in cancer sera. By the end of the sixties attitudes had changed because, it was argued, cancer cells must somehow differ from healthy cells because they escape from the control of normal cell regulators.
If they are different, they must secrete characteristic proteins, lipids, or other (macro)molecules which normal cells do not and so the search for tumor indicators was begun.
In 1957 BJÖRKLUND and associates (1) identified a substance which seemed to be directly associated with the presence of tumors (2). He called this substance TPA, short for Tissue Polypeptide Antigen.
In 1963 another tumor indicator called alpha-fetoproteine (AFP) was discovered. The Russian research worker G.I. ABELEV (3) of the N.F. Gameleya Institute for Epidemiology and Micro-biology in Moscow demonstrated the increased levels of AFP in mice with hepatoma implants (3).
In 1964 TATARINOV (4) demonstrated the presence of AFP in patients with liver tumor. Furthermore ARSELEV (6) and MASOPUST (7), working independently, succeeded in demonstrating the link between AFP and cell tumour of the testes and ovaries. Pathologically high levels of AFPIn 1965 Ph. GOLD and S.O. FREEDMAN (4) of the McGILL University Medical School published their first results on a new type of tumor indicator, referred to as CEA or Carcinoembryonic Antigen. At first they thought that the new indicator was only associated with colo-rectal tumours, but later on they were able to demonstrate that CEA could be associated with all tumors.
Another tumor indicator, now known as the Tennessee Antigen (5) was isolated by Tommije JORDAN of the JCL Clinical Research Corporation of Knoxville.Yet another tumor indicator is the so-called B-protein, isolated by Edsel T. BUCOVAZ. A whole series of enzymes and hormones which can be found in large quantities in the sera when specific cancers are present have long been in use and received FDA approval in 1976.
Prostatic acid phosphatase is a well characterized isoenzyme found in high concentrations in cancer of the prostrate.
Human chorionic gonadotrophin (HCG) is the hormone which can be found in higher concentrations in pregnant women, and in cancer of the uterus and (some cancers) of the testes.
Glycoprotein thyroglobulin or calcitonin is found in some cancers of the thyroid.
Creatine kinase is an enzyme which is found in high concentrations in patients with myocardiac infarction or in tumors of the smooth muscles of the pelvis and lungs.
Lactate hydrogenase is encountered in leptomeningial carcino-matosis.
Finally Gamma-glutamyltranspeptidase; S-Nucleotidase; and Leucineaminopeptidase are all found in liver tumors.
The trend towards early diagnosis with the help of tumor indicators has thus received considerable encouragement and is in fact irreversible.
The detection of two or more specific tumor indicators in the sera of patients, means that a tumor can be diagnosed with almost absolute certainty.
Other more specific tumor indicators are still in the experimental stage. These include:
Beta-glucuronidase, a normal enzyme, which when present in abnormal quantities indicates leptomeningeal carcinomatosis.
Breast-cyst fluid protein (BCFP) is a tissue antigen which appears in breast cancer.
Colon mucoprotein antigen (CMA) is a colon specific substance.
Galactosyl transferase isoenzyme II (GT-II) is a normal antigen which appears to be closely linked to cancers of the pancreas, stomach and colon.
Pancreatic oncofetal antigen (POA) is a fetal protein with a high correlation to cancers of the pancreas.
Prostate specific antigen (PSA) is a new prostate specific indicator.
Zinc glycinate marker (ZGM) is a tissue antigen closely related to gastro-enteric cancers.Not so long ago, (in January 1981) E.A. DAVIDSON and S.D. BOLMER respectively of the Pennsylvania State University College of Medicine and MIT, isolated the sialoglycoprotein, which appears to be very promising because of its marked specificity for cancer.
Tumor related antigens
A tumor-related antigen is a substance which may be partially or exclusively associated with cancer. The word antigen is in fact not so suitable here. The term was chosen because these molecules were largely determined using immunological methods. Tumor related material, substance, marker or indicator would have been better.
TPA Tissue Polypeptide Antigen
BJÖRKLUND attempted to formulate an immune serum on the basis of 56 different sorts of tumors. This was injected into a horse which produced antibodies to it. These antibodies appeared to be selectively cytotoxic in vitro to human tumor cells, leaving the healthy cells unaffected.
Further research into tumor tissue brought the presence to light of an antigen which is not present in normal tissue. This was a small protein, the structure of which could not be entirely determined.
This protein, dubbed TPA, or Tissue Polypeptide Antigen, is a non-compound membrane protein. It possesses no sugars, lipids or prothesis groups. Part of the protein's series of amino acids is known and the synthetic peptides which match the protein's series of amino acids are capable of forming compounds with antibodies against the entire antigen complex (8).
TPA fluoresces in ultra-violet light. It can be isolated from human tumours by a highly complex series of processes, which includes several chromotographies.
It is therefore necessary for diagnostic purposes that the indicator, in this case TPA, is secreted into (one of) the various sera in which it can be detected. Another requirement is the presence of a mechanism for introducing the indicator in the serum. For example, the indicator may be continually secreted throughout the life of the cell, or only during a certain stage of its development or when it dies.
TPA appears only to be synthesized during the S-phase of cell division and to be secreted the rapidly dividing tissue.
As many tumors are characterized by alternating periods of rapid and slow growth (or even spontaneous regression) TPA (like CEA, discussed elsewhere in this book) is a significant indicator of tumor development and is therefore helpful when observing the results of certain therapies. As the tumor-related antigen is present in very small amount in normal body fluid, a threshold level must be determined below which 95 % of healthy human beings fall. For TPA this value is 85µ/l (1 mg pure TPA roughly corresponds to 4 µ).
In contrast to most tumor-related antigens, TPA is a general tumor indicator and can be found in virtually all malignant growths. In tests TPA could be isolated from biopsies of forty or so neoplastic growths.
MENENDEZ-BOTET, OETTGEN and others (9) were able to demonstrate in laboratory work a correlation between certain levels of TPA and tumors and achieved the following percentage scores for accuracy: of the breast 86 %, of the lung 89 %, colorectal 87 %, of the prostate 75 %, of the bladder 75 %, of the uterus and pelvis 86 %, of the stomach 77 %, and of the pancreas 100 %. 71 % accuracy was achieved for melanoma, and 100 % and 80% for leukemia and sarcoma respectively.
LUTHGENS and SCHLEGEL (10) for their part obtained the following percentage figures for various tumors : of the breast 89%, of the lung 88%, colorectal 87%, of the uterus and pelvis 75%, and of the testes 64%. 81% accuracy was achieved for melanoma, and 92% and 100% for leukemia and hypernephroma respectively.Method of TPA Detection
In the experimental stage the presence of TPA was ascertained from the cytotoxic effect of the antibodies on TPA in vitro. This difficult, multi-stage, and basically impractical method was subsequently replaced by the hemaglutination inhibition or "HI" technique, which makes use of the principle of the series saturation of TPA specific antibodies. This technique too was later abandoned in favour of PROLIFIGEN ® TPA (I125) radioimmunoanalysis (11), which is still used today. This technique makes use of the radioisotope marker I125. Marketed in kit form by Sangtec Medical AB of Sweden, all well-equipped laboratories should now be capable of determining TPA.
The Pregnancy Proteins
Pregnancy proteins are proteins found in pregnant woman and which except during pregnancy are normally not present at all or only in very small amounts. The level of many similar pregnancy-related substances such as AFP and CEA is much higher in malignant diseases and were therefore investigated for use as tumor indicators and are now used as such.
Pregnancy and cancer are similar in that during both (growth) processes the body's immune reaction is suppressed, so that the exogenic antigen (the foetus or the cancer cell) is not recognized as such and attacked. According to GORDAN and CHARD (12), who in 1979 formulated new hypotheses in this respect, it is highly probable that these pregnancy proteins (chiefly in the form of beta1-glycoprotein and alpha2-glycoprotein) have the ability to suppress the immune system and play a role in immune tolerance. These proteins may also play a role in the carbohydrate metabolism, the transportation in the body of certain substances (such as steroids and iron) and hemostase (13).
The pregnancy proteins are divided into several groups: proteins specific to pregnancy, proteins related to pregnancy, fetal proteins, and others.1. Pregnancy specific proteins as tumor indicators
These pregnancy specific proteins are not normally present in the serum except in pregnancy. It is assumed that they are generated within the placenta, chiefly in the trophoblast, and that from there they are released into the blood (14).
a. beta1-glycoprotein (SP 1)
Numerous research workers have concentrated their projects on pregnancy-specific proteins and proceeded to name them. Studies of these proteins with a view to obtaining pregnancy and tumor indicators only intensified in the seventies, specifically in 1971, when Dr BOHN of the Behring Institute succeeded in isolating and describing them (16). THORNES (17), working in 1958, gave the general name of P protein to this pregnancy specific protein. Since then numerous names have been given to the protein. TATARINOV referred to it first as pregnancy specific beta1-globulin (1970), then calls it successively trophoblast beta-globulin or TBG (1975), pregnancy specific beta1-globulin (1976), trophoblast specific beta1-globulin (1977), and finally settling in 1978 on trophoblast specific beta1-glycoprotein (18). BOHN, who isolated the protein in 1971, first called "Schwangerschaft spezifische beta1-glycoproteine (SP 1) (19). LIN and HALBERT refer to pregnancy associated plasmaprotein-C (PAPP-C) (20), while HORNE and associates talk about pregnancy specific beta1-glycoprotein (PS G) (21), as does SEARLE and associates, although the latter also use the name beta1-glycoprotein (22).
The pregnancy specific protein SP 1 is a glycoprotein rich in carbohydrate (according to BOHN 29.3% carbohydrates), with a molecular weight of about 100,000 dalton (24). The protein is found in the cytothrophoblast and is concentrated in the synctiotophoblast, as BOHN and SEDLACEK (25), HORNE and others (26), LIN AND HALBERT (27), and TATARINOV and others (28) were able to show. Beta1glycoprotein was also found by HORNE and others (29), JOHNSON (30), and TATARINOV and others (31) in the synctiotrophoblast of hydrativermemola (32) invasive mola, chorio-carcinoma, as well as in the cells of malignant testesteratoma. HORNE (33) also demonstrated the presence of SP 1 in the cytoplasma of non-trophoblast tumors of the breast and the gastroenteric canal. SP 1 is also found in non-trophoblast neoplasms such as carcinoma of the testes, lungs, and ovaries (34). It appears that a minimum level of hardly 1-3µg/l (!) of beta1-glycoprotein in males and non-pregnant females is enough to indicate trophoblast tumor. The detection of SP 1 is thus an extremely powerful diagnostic tool and means of monitoring progress. The pathological limit for non-trophoblast tumor is slightly higher (40-50 µg/l) (36).
In order to gain some idea of the proportions, for marked bladder mola, massive mola and choriocarcinoma HORNE and BREMNER determined values of beta1-glycoprotein of 2260, 79,000 and 491 µg/l respectively (35).The enzymimmunoassay method is ideal for measuring the level of SP 1 and preferable to radioimmunoassay (37). As non-isotopic immunoassay the enzymimmunoassay is easy to perform in any laboratory and moreover has the same degree of sensitivity as the RIA method and shows a very good correspondence to the latter (38).
Enzymimmunoassay: HOECHST sells an ELISA (enzym-linked immunoabsorbent assay) assay for determing SP 1 levels. Other tests include ENZYGNOST® - SP 1.
HOECHST also makes a radioimmune assay, RIA-gnost®-SP 1.
b.Human Chorionic Gonadotrophine (HCG)
HCG or growth hormone is a glycoprotein which is synthesized in the synctiotrophoblast of the placenta (39). It consists of two non-identical and non-covalently bonded sub-units which are referred to as the alpha an beta chains. The alpha sub-unit is identical to LH, FSH and TSH (i.e. luteinizing, follicle-stimulating, and thyroid-stimulating hormones). It is the beta-subgroup (referred to below as beta-HCG or b-HCG) which confers biological and immunological specificity on these glycoprotein hormones.
The majority of pregnancy tests detect HCG, a substance which appears very early on in pregnancy (between the 7 and 14th days after conception). Apart from its appearance in pregnancy, HCG is, like beta1-glycoprotein, found in certain neoplasms, mainly of the trophoblast, and in tumors of the testes (41).
HCG detection (or rather b-HCG detection) has thus been proved to be an effective way of detecting the aforementioned cancers at an early stage, and of monitoring therapy. As in certain cases of bladder mola and chorionic carcinoma only SP-1 and no b-HCG is found (42), it appears to be advisable to combine the tests for SP-1 and b-HCG.
In germ-cell tumors (tumor of the testes) with choriocarcino-matosic components or with syncytial giant cells AFP (alphafeto-protein, see below) is also found, as well as b-HCG and SP-1, and a combination of tests appears to be most suitable.
The Navarro Test
There is also an RIA for the specific detection of b-HCG with a sensitivity of 1-10 I.E. per litre and which avoids all possible interference with LH, FSH and TSH (45): RIA-b-HCG-Serono.
c. Diaminoxidase (Histaminase) DAO
A diamino-oxidase active enzyme undergoes enhanced synthesis in placenta, largely because its histamine substrate is produced in greater quantities in the foetus (46).
For this reason DAO levels give an indication of the health of the foetus (47).
No increase in the DAO can, however, be detected for trophoblastic tumors. On the other hand, this enzyme is present in increased quantities in other malignant disease, particularly in the ascites fluid of patients with ovarian carcinoma.
d. Thermostable alkaline phosphatase
The placenta synthesizes an isoenzyme of alkaline phosphatase. Known as thermostable alkaline phosphatase or TSAP this isoenzyme can be detected in the blood serum of pregnant women (49).
A special isoenzyme of alkaline phosphatase has been detected in tumor patients, the characteristics of which closely resemble those of placental alkaline phosphatase. This variant was first detected in a patient with a bronchial carcinoma and was given the name Reagan isoenzyme (50). High concentrations of the Reagan isoenzym are associated with a variety of tumors, particularly pancreatic, bronchial, and mammarian carcinoma (51).
Special kits are available for the detection and quantification of TSAP (52).
e. Other proteins specific to pregnancy but not to neoplasms
Other proteins specific to pregnancy but which are not associated with cancer are given here for the sake of completeness.
These are: Human Placenta Lactogen (HPL, or Human Chorionic Somatomammotrophin) (52), cystinamino-peptidase (CAP or oxytocinase) (53), 17-beta-hydroxy-steroid-dehydrogenase (17-b-HSD) (54), and A and B plasma protein (PAPP-A and PAPP-B) (55).
2. Pregnancy-related proteins as tumor indicators
These proteins are not generated in the placenta but elsewhere and are found in all sera. Their concentrations, however, rise steeply in pregnancy. The levels of pregnancy-related proteins also rise under the influence of other causes, such as oral contraceptives (oestrogens) and certain inflammatory diseases (56).
a. Sex-hormone bonding globulin (SP-2)
Traces of SP-2 (steroid-bonding beta-globulin) are found in all sera (57). It serves as a transport protein for steroids. Until the 28th week of pregnancy the level of SP 2 increases steeply (58). This increase is probably triggered by the steroids, as the SP-2 level also increases under the influence of the oestrogen contraceptives (59). A direct link has been uncovered between SP-2 levels and bonding capacity and the presence of oestrogen receptors in tumor tissue in patients with cancers of the breast or prostate. By detecting and measuring SP-2 in the body the hormone dependency of the tumor can be established and in conventional approaches a (more) effective way of using hormones or cyto-toxic therapy can be sought (60).
SP-2 levels can also be measured by means of Rocket-immunoelectrophoresis or other methods which, after fission by filtration or electrophoresis, allow the radioactive steroid bonded to the protein to be traced.
b. Alpha2-glycoprotein (SP-3) (Alpha2PAG)
Traces of this normal plasma protein are to be found in nearly all sera (61), but may rise to 1000 mg/l in pregnancy (62).
SP-3 levels also rise sharply when oestrogen preparations are administered (63).
Although increased levels of SP-3 in association with certain benign growths (64), the determination of the SP-3 level is very important in monitoring therapy and the early diagnosis of relapse and the metastasis of malignant disease. A direct link between SP-3 levels and the advance of malignant disease has been clearly established (65). A significant drop in the SP-3 level was noted in breast cancer patients who responded to therapy, while when the cancer metastased SP-3 levels were seen to increase. The latter increase is the more remarkable as it occurred prior to themetastasis being clinically observed (66). Similar links between the SP-3 level and advance of other malignant disease could also be demonstrated experimentally. BAUER, GROPP and BOHN have pointed out the connection between SP-3 and bronchial carcinoma (67), BAUER, DEUTSCHMANN, PETER and BOHN have done the same for melanoma (68), while BAUER and KRAUS did the same for gynaecological carcinomas (69).An ELISA enzymeimmunoassay for the determination of the SP-3 is now available as well as Rocket-immunelectrophorese and RIA.
3. Fetal Proteins
Fetal proteins are usually produced by the foetus and are present in higher quantities chiefly in the fetal serum. When pathological developments overtake the foetus they can also be detected in the mother's serum. As these proteins are of embryonic origin, the information for their synthesis must already be present in human cells. It has been that that in the event of cancergenosis these fetal proteins are synthesized in large quantities and enter the bloodstream.
a. Alpha-fetoprotein (AFP)
AFP is an acid glycoprotein with a molecular weight of approximately 70,000 dalton which is synthesized in the gastroenteric canal, the liver and yolk sac in the embryonic stage, rising in the fifth week of pregnancy to an AFP level in the fetal serum of 2,000,000 I.E. per ml (3g per l).
In healthy (non-pregnant) subjects the AFP level lies below 7 I.E. per ml (10 µg per l). In patients with acute viral hepatitis there are temporary increases of the AFP level (to about 70 I.E. per ml) (71). Increased AFP levels ranging from 80 to 800 IE per ml have been observed in cirrhosis of the liver, chronic aggressive and chronic persistent hepatitis, alcohol hepatitis, and fatty liver (72).For the sake of completeness we should also mention that pathological levels of AFP occur in patients suffering from ataxia teleangiectasia (73) and hereditary tyrosinemia (74) (a congenital metabolic disorder).
The physiological function of AFP has as yet not been explained. It has been suggested that it may have a role in defending the foetus from maternal oestrogens or the mother's immune system.
Another hypothesis which wins some acceptance in professional circles is that AFP is a fetal form of albumen or a special transport protein (75). Whatever the case may be, a remarkable degree of correlation was discovered in 1972 between raised levels of AFP in the amniotic fluid of pregnant women and severely malformed foetuses with spina bifida aperta and open neural tubes (76). Since then the detection of AFP has assumed considerable significance, as it can give a useful early warning of malformation and permit early therapeutic termination of pregnancy (77). A high AFP level is also a sign of malignant tumor. For example, 80 to 95 % of hepatoma (liver carcinoma) have the ability to synthesize AFP in the tumor tissue, which enters the serum and may even enter the ascites and pleurus exudate (78).
Only in 5 to 15 % of hepatoma does the AFP level remain below normal (79). In certain teratogenic tumors, such as testes and ovarian cancers the AFP level rises, as ABELEV showed in 1967. These AFP levels may rise as much to 20,000 I.E. per ml (80).
AFP values of 1500 I.E. per ml have been observed in tumors of the G.I. canal (81) while above normal AFP levels have been observed in mammarian, prostrate, bronchial, and cervical carcinoma (82).
The most pronounced rise, however, is in the AFP level in primary liver carcinoma and germ carcinoma of the testes and ovaries. AFP detection is therefore an essential method of diagnosing these types of cancer. Furthermore AFP detection is important for differential diagnosis, monitoring therapy, and the early diagnosis of relapse in a variety of other cancers.
Because of the high degree of sensitivity required - normal values for AFP levels lie around 7 I.E. per ml or 10 g per litre - only radio and enzymimmunological methods can be considered (83).
The HOECHST AG corporation of D-6230 Frankfurt am Main 80, FRG markets RIA-gnost®-AFP and Enzygnost®-AFP. The Institut de Recherches sur le Cancer, PO box 311, F57020 LILLE, C·Ç·dex, has developed an AFP detection method based on radioimmunoelectrophoresis with
(acknowledgements to AXELSEV et al.)
Carcino-embryonic Antigen (CEA)
CEA is an oncofetal antigen and has proved useful for detecting and especially for monitoring not only colorectal tumors (as GOLD and FREEDMAN originally thought) but lung and breast cancers as well. This has been clinically confirmed by various researchers, including CONCANNON et al., GROPP, LEHMANN and HAVEMANN, LAURENCE et al., LO GERFO, KRUPEY and HANSEN, VINCENT and CHU (84).
The detection of CEA has proved highly effective in discovering metastases as demonstrated by GROPP and LUSTER (85). In bronchial carcinoma patients with a 50 % increased CEA level, 80 % displayed metastasis while only 8 % did not. It can thus be assumed that an increased CEA level is ten times more indicative of metastased than local cancers.Some cancer researchers such as BJORKLUND and T. CHU of the Roswell Park Memorial Institute have pointed out that diagnosis can be considerably improved by running tests for CEA and TPA together, and possibly combining them with an erythrocyte sedimentation test (ESR).
LUTHGENS and SCHLEGEL et al. (87) have investigated the relationship between CEA and TPA in 176 breast tumor patients. It was found that positive diagnoses (pathological condition) could be made with 96% accuracy while negative diagnoses (non-pathological) could be made with 94% accuracy. A study of colorectal cancers carried out at the Mayo Clinic subsequently confirmed these results (88). Furthermore LUTHGEN and SCHLEGEL et al. (89) investigated the reliability of about twenty cancer test and compared with the combined CEA-TPA test. They were able to show that the TPA-CEA combination offered the most accurate picture of clinical pathology, better, in fact, than all the other test together. In healthy blood the correlation between TPA and CEA is virtually non-existent.
ANDREN-SANDBERG and ISAACSON (90) investigated the combination of TPA and ESR in colorectal cancers and here too found a very low degree of correlation.Tennessee Antigen
Tennessee Antigen is a glycoprotein with a mass of 100,000 daltons. JORDAN devised a test for detecting Tennessee Antigen (by making use of its ability to inhibit hemaglutination - similar in fact to the H.I. technique referred to above, page ...). This test is now commercially available from the Sherwood Medical Institute, St. Louis.
Clinical research at SHERWOOD has shown that the test can detect 75 % of lung cancers, 79% of stomach cancers, and 82% of colorectal and pancreatic cancers at an early stage. Incorrect positive diagnosis occurs in only 8% of cases. Persons suffering for non-malignant lung or gastroenteritic disease may also show a positive reaction.
B-Protein
Edsel T. BUCOVAZ and associates (91) have established that a yeast protein, known as "co-enzyme A synthesizing protein complex", forms a compound specifically with B-proteins. By marking yeast proteins with a radioisotope it is possible to trace B-protein in the blood. B-protein has a mass of 120,000 daltons and is closely related to the spleen in animals and probably in humans as well.
BUCOVAZ's hypothesis is that the spleen produces B-protein as a reaction to a tumor, regardless of where it is. The usefulness of such a general cancer indicator is obvious. BUCOVAZ has been able to obtain an 87% accurated positive diagnosis rate with only 8% incorrect positive diagnoses. The test is 100% accurate in detecting relapses when confirmed cancers are being treated.
Sialoglycoprotein
Sialoglycoprotein is the latest tumor antigen to be isolated. It is a protein which is bonded to sugar residues and a sugarlike compound known as sialic acid. This protein resembles no other and is furthermore closely related to malignant cancer.
DAVIDSON and BOLMER have developed a radio-immunoanalysis which can be used to detect sialoglyco-protein and which by January 1981 had already been tried on 300 blood samples from cancer patients and 300 samples from health patients.
The presence of cancer was determined with 96% accuracy while only 2% of positive results (antigen found in apparently healthy blood) were incorrect.
Sialoglycoprotein also appears to be related to a wide range of tumors as it also capable of indicating sarcoma, carcinoma, melanoma, and Hodgkin's disease.
The WARNER-LAMBERT company of Morris Plains, N.J. (USA) has received FDA approval and hopes to be able to bring this very promising test to market very shortly, despite the limited clinical testing, itself an indication of the company's confidence in the test.
DAVIDSON is currently engaged in trying to determine the cell structure of sialoglycoprotein in the hope of being able to construct a model which can be used to work out a more sensitive test based on monoclinal antibodies.
Prostate-specific Acid Phosphatase (PAP)
Prostatic acid phosphatase is a glycoprotein belonging to the group of acid phosphatases and is synthesized in prostate epithelium (92). This secretory enzyme (EC 3.1.3.2.) (93) is present in normal seminal plasma, and to a lesser extent in urine, although only tiny traces are to be found in the serum of healthy people, has a molecular weight of about 100,000 dalton (94).
As long ago as 1938 GUTMAN and GUTMAN (95) pointed out the increased serum activity of acid phosphatase in metastasing prostate carcinoma.
The determination of total serum acidic phosphatase using functional identification techniques (enzymatic function) was, however, not cancer-specific for prostate carcinoma (96), as the total of acid phosphatase is a mixture of five isoenzymes from thrombocytes, erythrocytes, RES cells (liver, spleen), bones and prostate gland. Furthermore this enzymatic examination technique is subject to interference from things such as temperature, pH, hemolysis, and medicines. An attempt by FISCHMANN and LERNER (97) in 1953 to improve the specificity of the test by differentiating the tartrate-labile part of the acid phosphatase, did actually result in increased specificity but remained unsatisfactory, largely because the prostate gland isoenzyme only produces the half of the tartar-inhibiting component. FISCHMANN and LERNER (98) were, however, the first to link high PAP levels to prostate carcinoma.
SCHULMAN, MAMROD, GONDOR and SOANES (1964) (99), ABLIN, BRONSON, SOANES and WITEBSKY (1970) (100) suggested the immunological differentiation of PAP and in so doing opened the way for immunochemical identification methods, such as radioimmunoassay, developed in 1975 by FOTI, HERSCHMAN and COOPER (101), and the enzyme immunoassay, introduced in 1979 by GRENNER (102) and CHOE, ROSE, KAROL, and PONTES (103). These new research methods were to make the specificity of the test more satisfactory. These developments also got round the problems of the influence of temperature, pH, hemolysis, and medication on test results (104). These methods detect prostate acid phosphatase by their structural (rather than their functional) properties (105), which allows a high degree of sensitivity, as well as great specificity (106).Healthy people have very low PAP levels. COOPER, BAUER and DATI (107) found PAP levels of 1.0 g per litre in tests of 243 male and female subjects under 40 years old. JACOBI and associates (108) found normal values of 0.8 g per litre in 96 males and 98 females, while FLÜCHTER, BICHLER, and HARZMANN (109) found physiological values of 0.9 g per litre in 89 males. Slightly higher levels have been found in patients with non-malignant prostate disease, even so 95 % of examined patients showed PAP concentrations of lower than 1.8 g per litre (110). The pathological limit of prostate carcinoma has thus been set at 2.0 g per litre (being 1.8 g per litre plus 0.2 g per l to take the sensitivity of the method into account). A value under these limits does not necessarily mean that cancer can be excluded. What can be said with certainty though is that values above 2.0 g per litre always indicate prostate cancer (111).
The PAP test is also an effective way of monitoring the progress of therapy and diagnosing metastasis at an early stage (112).
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Foot-notes
(1) BJÖRKLUND, B. and BJ·ô·RKLUND, V., Antigenicity of pooled human malignant and normal tissues by cytoimmunological technique: Presence of an insoluble heat labile tumor antigen, Int. Arch. Allergy, 10, pages 153-184, (1957)
BJÖRKLUND, B. LUNDBLAD, G. and BJÖRKLUND, V., Antigenicity of pooled human malignant and normal tissues by cytoimmunological technique: Nature of tumor antigen, Int. Arch. Allergy, 12, pages 241-261. (1958)(2) BJÖRKLUND, B. (ed.) Immunological Techniques for Detection of Cancer, Bonniers, Stockholm, (1972)
BJÖRKLUND, B. On the Nature and Clinical Use of Tissue Polypeptide Antigen (TPA), Tumor Diagnostik, 1, pages 9-20 (1980)
HOLYOKE, E.D. and CHU, T.M. Tissue Polypeptide Antigen, in HERBERMAN R.B. and McINTIRE, (ed.) Immunodiagnosis of Cancer, Marcel Dekker, New York and Basle, pages 513-521 (1979)(3) ABELEV, G.I., Alpha-fetoprotein in Ontogenesis and its Association with Malignant Tumors, Adv. Cancer Res., 14, pages 295-358 (1971).
(4) GOLD Ph. and FREEDMAN, S.O., Specific Carcinoembryonic Antigens of the Human Digestive System, J. Exp. Med., 122, pages 467-481 (1965)
(5) POTTER, Th. P. jr., JORDAN, T., JORDAN, J. and LASATER, H., Tennagen, a New Tumor Associated Antigen, in NIEBURGS, H.E. (ed.), Prevention and Detection of Cancer, part II (Detection), Marcel Dekker, New York, pages 467-490 (1978)
(6)
(7)
(8) WIRKLUND B., Studies on Tissue Polypeptide Agent (TPA) and its Antigenic Determinant, Chem. Commun Univ. Stockholm, 1. Dissertation. (1980);
REDELIUS P., Studies on the Primary Structure of Tissue Polypeptide Antigen (TPA) Chem. Commun Univ. Stockholm, 2. Dissertation. (1980);
REDELIUS P. LÜNING B. and BJÖRKLUND B. Chemical Studies on Tissue Polypeptide Antigen (TPA). II: Partial Amino Acid Sequence of Cyanogen Bromide Fragments of TPA subunit B_1., Acta Cham. Scand., B 34, pps. 265-273 (1980);
LÜNING B., WIRKLUND B., REDELIUS P. and BJÖRKLUND B., Biochemical Properties of Tissue Polypeptide Antigen (TPA), Biochim. Biophys. Acta, 624, pps. 90-101 (1980).(9) MENENDEZ-BOTET CELIA J., OETTGEN H.F., OINSKY C.M. and SCHWARTZ, M.K., A Preliminary Evaluation of Tissue Polypeptide Antigen in Serum or Urine (or both) of Patients with Cancer or Benign Neoplasms, Clin. Chem., 24, pps. 868-872. (1978)
(10) LÖTHGENS M. and SCHLEGEL G., CEA + TPA in der klinischen Tumordiagnostik, insbesondere des Mamma-Karzinoms, Tumor Diagnostik, 1, pps 63-77. (1980)
(11) PROLIFIGEN® is a trade name of Sangtec Medical AB, Sweden.
(12) GORDON Y.B. and CHARD T., The specific proteins of the human placenta, in (ed.) KLOPPER A. and CHARD T., Placental Proteins, Springer Verlag, Berlin, 1979, p. 1.
(13) ibid.
(14) BOHN H., Placental and pregnancy proteins, LEHMANN, F.G. (ed.), Carcino- Embryonic Proteins, Vol. I, Elsevier Press, Amsterdam, 289, 1979.
BOHN H., and DATI, F., Placental and pregnancy proteins, in RITZMANN, S.E. (ed.).( ) Protein abnormalities, Diagnostic and clinical aspects, Little, Brown and Company, Boston, 1982.
KLOPPER A., SMITH R., and DAVISON I., The measurement of trophoblastic proteins as a test of placental function in KLOPPER A. and CHARD T. op cit. 23, 1979.
DATI F., Schwangerschaftsproteine: Diagnostische Bedeutung in der Schwangerschaftsüberwachung and Tumordiagnostiek, MTA-Journal 6, 238, 1981.(16) BOHN H. Nachweis und Charakterisierung von Schwangerschafts-proteinen in der menslichen Plazenta, sowie die quantitatieve immunologische Bestimmung im Serum Schwangerer Frauen, Arch. Gynaekol., 210, 440, 1971.
(17) THORNES
(18) TATARINOV Y.S., Identification immunochimique de la beta1globuline de la zone de grossesse dans le serum de malades atteintes de tumeurs trophoblastiques, Int. J. Cancer, 14, 548, 1974.
TATARINOV Y.S., FALALEWA D.M. KALASHNIKOW V.V. and TOLOKNOV B.O., Immunofluorescent localization of the human pregnancy-specific beta-globulin in placenta and choriepithalioma, Nature, 260, 263, 1976.
TATARINOV Y.S., and SOKOLOV A.V., Development of a radio-immunoassay for pregnancy-specific beta1-globulin and its measurement in serum of patients with trophoblastic and non-trophoblastic tumours, Int. J. Cancer, 19, 161, 1977.
TATARINOV Y.S., A new placental protein test for the presence and identification of trophoblastic tumors, Antibiotics Chemother., 22, 125 1978.
TATARINOV Y.S., Trophoblast-specific beta1-glycoprotein and its clinical application in tumors, Carcino-embryonic Proteins, Vol. I, 313 Elsevier, 1979.(19) BOHN H. Nachweis und Charakterisierung von Schwangerschafts-proteinen in der menslichen Plazenta, sowie die quantitatieve immunologische Bestimmung im Serum Schwangerer Frauen, Arch. Gynaekol., 210, 440, 1971.
(20) LIN T.M. and HALBERT S.P., Placental localization of human pregnancy-associated plasma proteins, Science, 193, 1249, 1976.
(21) HORNE C.H.W., TORALER C.M., PUGH-HUMPHREYS R.P.G., THOMSON A.W., BOHN H. Pregnancy-specific beta1-glycoprotein: a product of the syncytiotrophoblast, Experienta, 32, 1197, Basle, 1976.
HORNE C.H.W., Production of pregnancy specific beta1-glycoprotein by non-trophoblastic tumours, Protides Biol. Fluids 24th Colloquium, 1976, 567.(22) SEARLE F., BAGSHAWE K.D., DENT J., LEAKE B.A., Serial measurement of pregnancy specific beta1-glycoprotein (beta1SP1) in patients with trophoblastic disease, Scand. J. Immunol., 8, Suppl. 8, 587, 1978.
(23) BOHN H., Pregnancy specific beta-globulin SP 1, Scand. J. Immunology, 7, Suppl. 6, 119, 1978.
(24) BOHN H., Isolierung und Charakterisierung des Schwangerschafts-spezifischen beta1-Glycoproteins, Blut, 24, 292, 1972.
(25) BOHN H., and SEDLACEK H. Eine vergleichende Untersuchung van Plazenta spezifischen Proteinen bei Mensch und Primaten, Arch, Gynaekol., 200 105, 1975.
(26) HORNE and others op cit.
(27) TATARINOV and others op cit.
(28) LIN T.M., HALBERT S.P. op cit.
(29) HORNE C.H.W. and others op cit.
(30) JOHNSON S., Pregnancy-specific beta1-glycoprotein in plasma and tissue extract in malignant teratoma of testis, Brit. Med. J. I., 951, 1977.
(31) TATARINOV Y.S. and others op cit.
(32) Mola is a pathological condition resulting from the uncontrolled circulation of chorionic villi in a pathological ovum, characterized by trophoblastic proliferation.
(33) HORNE C.H.W. op cit.
(34) LANGE P.H., BREMNER R.D., HORNE C.H.W. VESSELIA R.L. and FRALEY E.E., Is SP 1 a marker for testicular cancer? Urology, 15, 252, 1980.
SEARLE F., LEAKE B.A., BAGSHAWE K.D., DENT J. Serum-SP 1, pregnancy-specific beta1-glycoprotein in choriocarcinoma and other neoplastic disease, Lancet, 1, 579, 1978.
HORNE C.H.W. and BREMNER R.D., Schwangerschaftsspezifisches beta1-Glycoprotein (SP 1): ein Tumormarker, Laboratoriumsblätter, 2, 81, 1982.(35) RUTANEN E.M., SEPPÄLÄ M. Pregnancy-specific beta1-glycoprotein in trophoblastic disease, J. Clin. Endocrinol. Metab., 50, 57, 1980.
(36) HORNE and BREMNER, op cit.
(37) GRENNER G., Enzymimmunoassay zur Bestimmung des schwangerschafts-spezifischen beta1-Glykoproteins (SP-1), Fresenius Z. Anal. Chem., 209, 99, 1978.
(38) In pregnancy and particularly during the last months, where high concentrations of SP 1 can be observed, less sensitive and simpler immunological methods can be used, such as radioimmunodiffusion (using the HOECHST product M-PARTIGEN SP-1), Rocket-immunoelectrophoresis and laser-nephelometry.
(39) VAITUKAITIS J.L., ROSS G.T., BRAUNSTEIN G.D., RAYFORD P.L. Gonadotrophins and their sub-units: basic and clinical studies, GREEP R.D. (ed.), Recent Progress in Hormone Research, Academic Press, New York, 289, 1976.
(40) ibidem
(41) JONES W.B., LEWIS J.L. LEHR M., Monitoring of chemotherapy in gestational trophoblastic neoplasm by radioimmunoassay of the b-sub-unit on human chorionic gonadotrophin, Am. J. Obstet. Gynaecol., 121, 669, 1975.
( ) ACKERMANN R. Immonologische Aspekte bei urologische Tumoren, Med. Klin. 75, 436, 1980.
SCHUSTER E. Messung von SP-1 und bHCG bei trophoblastischen und embryonalen Tumoren, Tumour Diagnostic, 2, 13,1981.
SCHUSTER E., WEPPLEMAN, B., Serum levels of SP-1 and b-HCG in choriocarcinoma and ovarian cancer, First International Congress on Hormones and Cancer, Rome, October 3 - 6, 1979.(42) RUTANEN E.M., SEPPÄLÄ M., Pregnancy-specific-beta1-glycoprotein in trophoblastic disease, J. Clin. Endocrinol. Metab., 50, 57, 1980.
(43) SCHUSTER, E. op. cit.
(44) LANGE P.H., BREMNER R.D., HORNE C.H.W., VESSELIA R.L., FRALEY E.E., op cit.
(45) VAITUKAITIS J.L., BRAUNSTEIN G.D., ROSS G.T. A radioimmunoassay which specifically measures human chorionic gonadotrophin in the presence of human luteinizing hormone, AM. J. Obstet. Gynaecol., 113, 751, 1972.
(46) LIN C.W., KIRLEY S.D. Human placental and tumor histaminase, in PEETERS H., (ed.) Protides of the Biological Fluids, Vol. 24, Pergamon Press, Oxford, 103, 1976.
(47) WARD H., WHYLEY G.A., MILAR M.D., Serial serum diamine oxidase estimations in normal singleton and twin pregnancies and in abnormal pregnancies, Am. J. Obstet. Gynaecol., 107, 1233, 1970.
(48) LIN C.W. KIRLEY S.D. op cit.
(49) BOYER S.H., Alkaline phosphatase in human sera and placenta, Science, 134, 1002, 1961.
(50) FISHMAN W.H., INGLIS N.R., STOLBACH L.L., KRANT M.J.A., Serum alkaline phosphatase isoenzyme of human neoplastic cell origin, Cancer Res., 28, 150, 1986.
(51) LEHMANN F.G., Immunological methods for human placental alkaline phosphatase (Reagan-isoenzyme), Clin. Chim. Acta, 65, 257, 1975.
(52) JACOBY B., BAGSHAWE K.D., A radioimmunoassay for placental type alkaline phosphatase, Cancer Res., 33, 2413, 1972.
(52) JOSIMOVIC J.B., MacLAREN J.S., Presence in the human placenta and term serum of a highly lactogenic substance immunologically related to pituitary growth hormone, Endocrinology, 71, 209, 1962.
LETCHWORTH A.T., Human placental lactogen assay a guide to fetal well-being, in KLOPPER A., (ed.), Plasma hormone assay in the evaluation of fetal wellbeing, Churchill Livingstone, Edinburgh, London and New York, 147, 1976.
LETCHWORTH A.T., SLATTERY M., DENNIS K.J., Clinical application of human placental-lactogen values in late pregnancy, Lancet I, 955, 1978.
LETCHWORTH A.T., CHARD T., HPL as a screening test for fetal distress and neonatal asphyxia, Lancet, I, 704, 1972.
SPELLACY W.N., BUHI W.C., SCHRAM J.D., BIRK S.A., McCREARY S.A., Control of human chorionic somato-mammotropin levels during pregnancy, Obstet. Gynaecol., 37, 567, 1971.
KNAPSTEIN P., MELCHERT F., Biochemische überwachung der Schwangerschaft, Gynaekologe, 1, 151, 1978.(53) TITUS M.A., REYNOLDS D.R., GLENDEMING M.B., PAGE E.W., Plasma aminopeptidase activity in pregnancy and labor, Am. J. Obstet. Gynaecol., 80, 112X, 1124, 1960.
HURRY D.J., TOVEY J.E., ROBINSON D.A., BEYNON C.L., COOPER K., Cystine aminopeptidase in normal and complicated pregnancies, J. Obstet. Gynaecol. Br. Commonw. 79, 788, 1972.
CHAPMAN L., SILK E., SKUPNY A., TOOTH E.A., BARNES A., Spectrofluorimetric assay of serum cystine aminopeptidase in normal and diabetic pregnancy compared with total oestrogen excretion, J. Obstet. Gynaecol. Br. Commonw. 78, 435, 1971.
WISSER, H. DETTMER, K., KNOLL, E., Die Bestimmung der Cystinaminopeptidase (Oxytocinase) mit einem ENI Fast-Analyzer, Z. Klin. Chem, Klin. Biochem., 14 435, 1976.(54) BREUER J., MEUSERS W., BREUER H., Enzym des Steroid-Stoffwechsels in Blut des Menschen, Z. Klin. Chem, Klin. Biochem., 6, 163, 1968.
BREUER J., PATT V., BREUER H., Enzym des Steroid-Stoffwechsels in Blut des Menschen, Z. Klin. Chem, Klin. Biochem., 7, 474, 1969.(55) LIN T.M., HALBERT S.P., KIEFER D.J., SPELLACY W.N., GALL S., Characterization of four human pregnancy-associated plasma proteins, Am. J. Obstet. Gynaecol., 118, 223, 1974.
SMITH R., BISCHOF P., HUGHES G. Studies on pregnancy associated plasma protein A in the third trimester of pregnancy, Br. J. Obstet. Gynaecol. 86, 882, 1979.
LIN T.M., HALBERT S.P., KIEFER D.J., Characterization and purification of the pregnancy-associated plasma protein B (PAPP-B) Inst.archs. Allergy Appl. Immun. 57, 294, 1978.
LIN T.M., HALBERT S.P., SPELLACY W.N., Pregnancy-associated plasma protein B (PAPP-B) in normal and abnormal pregnancies at term, Br. J. Obstet. Gynaecol. 86, 882, 1979.(56) BOHN H., Placental and pregnancy proteins, in LEHMANN, F.G. (ed.), Carcino- Embryonic Proteins, Vol. I, Elsevier Press, Amsterdam, 289, 1979.
BOHN H., and DATI, F., Placental and pregnancy proteins, in RITZMANN, S.E. (ed.). Protein abnormalities, Diagnostic and clinical aspects, 2. Aufl., Little, Brown and Co., Boston, 1982.(57) BOHN H., Isolierung, Charakterisierung und quantitatieve immunologische Bestimmung des Steroid-bindenden beta-Globulins, Blut, 29, 17, 1974.
(58) TOWLER C.M., JANDIAL V., HORNE C.H.W., BOHN H., A serial study of pregnancy proteins in primigravidae, Br. J. Obstet. Gynaecol., 83, 368, 1976.
(59) 60.
(60) 63-64.
(61) BOHN H., WINCKLER, W., Isolierung, Charakterisierung des schwangerschaftsspezifischen Alpha2-glycoproteins (Alpha2PAG) Blut, 33, 377, 1976.
(62) THAN G.N., CSABA I.F., SZABO D.G., An antigen associated with pregnancy, Lancet, II, 1578, 1974.
(63) BOHN H., WINCKLER, W.,
(64) BOHN H., Charakterisierung der schwangerschafts-assoziierten Glyko-proteine als akute Phase-Proteine, Arch. Gynäk., 213, 54, 1972.
(65) STIMSON, W.H. Variations in the levels of a pregnancy associated alpha-macroglobulin with the clinical course of patients, Lancet, I, 777, 1975.
(66) STIMSON, W.H. Variations in the levels of a pregnancy associated alpha-macroglobulin in patients with cancer, J. Clin. Path. 28, 868, 1975.
ANDERSON, J.M. Detection of mammary micrometastases by pregnancy-associated Alpha2-glycoprotein (PAG, Alpha2-PAG or PAM) and carcinoembryonic antigen (CEA), Europ. J. Cancer, 15, 709, 1979.(67) BAUER H.W., GROPP C., BOHN H., Schwangerschafts-assoziierten Alpha2-Glykoproteine (Alpha2-PAG) im Serum von Patienten mit Bronchialkarzinomen, Pl. Prax. Pneumol., 32,194, 1978.
(68) BAUER H.W., DEUTSCHMANN K.E.M., PETER H.H. and BOHN H., Pregnancy-associated Alpha2-glycoprotein in malignant melanoma, Europ. J. Cancer, 15, 123, 1979.
(69) BAUER H.W., KRAUS, H., Das Schwangerschaftasoziierte Alpha2-Glykoprotein (Alpha2-PAG) im Serum von Patienten mit gynäkologischen Karzinomen, Onkologie, 1, 180, 1978.
(70) LAMERZ R. et al; Fortschr. Med. 94, 702, 1976.
RUOSLAHTI E., SEPPÄLÄ M., Int. J. Cancer, 8, 374, 1971.
PURVES, L.R. et al. Cancer, 31, 578, 1973.
POLTERAUER, R. et al. Vienna. Klin. Wschr., 91, 201, 1979.
NORGAARD-PEDERSEN B., Human alpha-fetoprotein, A review of recent methodological and clinical studies, Scand. J. Immunol., 5, Suppl. 4, 1, 1976.
LEIGHTON P.C., GORDON Y.B., KITAU M.J., LEEK A.E., CHARD T., Levels of alpha-fetoprotein in maternal blood as a screening test for fetal neural tube defect, Lancet, II, 1012, 1975.(71) LEHMANN F.G. Das alpha-fetoprotein in der Diagnose des Hepatoms und teratogener Tumoren, Med. Labor., 30, 87, 1977.
LAMERZ R., Nachweis fetaler Antigene: Praktische Bedeutung für Diagnose und Nachzorge bei Malignomen, Therapiewoche, 28, 4081, 1978.
LEHMANN F.G., LEHMANN D., MARTINI G.A., Z. Gastroenterol., 11, 385,1973.
LAMERZ R. et al; op cit
GANZ M., JOLLER-JEMELKA H.I., GROB P.J., Schweiz. Med. Wschr. 109, 1324, 1979.(72) LAMERZ R. et al, op cit
LEHMANN F.G., op cit.(73) WALDMANN, T.A., McINTIRE K.R., Lancet, II, 1112, 1972.
(74) BELANGER, L. et al., Path Biol., 21, 449, 1973.
(75) URIEL J., DE NECHAND B., Gann. 14, 35, 1973.
RUOSLAHTI E., TERRY W.D., Nature, 260, 804, 1976.(76) BROCK, D.J.H., SUTCLIFFE R.G., Alpha-Fetoprotein in the antenatal diagnosis of anencephaly and spina bifida, Lancet, II, 197, 1972.
This sort of severe malformation of the foetus can be detected by means of an RAI analysis of AFP. As the positive results of such tests provide a very high level of erroneous results (according to IRANI of Nuclear Medical Systems Inc. of Newport Beach, California: 50 in 1000 women will have a positive reaction to AFP-RIA testing, but only two will be carrying a misformed foetus) the diagnosis must be confirmed by a short-wave sonograph and amniocentesis in order to reduce erroneous results to virtually nothing.(77) WEITZEL K.H., SCHUMANN K., SCHNEIDER I., Pränatale Diagnostiek angeborener Fehlbildungen durch Alpha-Fetoprotein-Bestimmung, Fortschr. Med. 97, 1005, 1979.
LEIGHTON P.C., GORDON Y.B., KITAU M.J., LEEK A.E., CHARD T. Levels of Alpha-Fetoprotein in maternal blood as a screening test for fetal neural-tube defects, Lancet, II, 1012, 1975.
LAURENCE K.M., Antenatal diagnosis in high-risk pregnancies and pregnancy screening for central nervous system malformation, in WEITZEL H.K., SCHNEIDER J. (ed.), Alpha-Fetoprotein in clinical medicine, G. Thieme Verlag, Stuttgart, 20, 1979.
BROCK D.J.H., SUTCLIFFE R.G. op cit.
WALD N.J., CUCKLE H.S., Antenatal screening for neural-tube defects, in WEITZEL H.K., SCHNEIDER J. (ed.), op cit.(78) POLOTERAUER R., et al., Wien. Klin. Wschr., 91, 201, 1979.
MASSEYEFF R., Gann Monogr. Cancer Res., 14, 3, 1973.(79) LEHMANN F.G., Das Alpha-Fetoprotein ... Med. Lab., 30, 87, 1977.
GANZ M., JOLLER-JEMELKA H.I., GROB P.J., Schweiz. Med. Wschr., 109, 1324, 1979.
McINTIRE K.R. et al., op cit.(80) BAUER H.W., KRAUS H., op cit.
LAMERZ R., FATEH-MOGHADAM A., Carcinofetale Antigene: I. Alpha-Fetoprotein, Klin. Wschr., 53, 147, 1975.(81) LAMERZ R., FATEH-MOGHADAM A., op cit.
POLTERAUER R. et al., op cit.
GANZ M., JOLLER-JEMELKA H.I., GROB P.J., op cit.
LAMERZ R., Nachweis fetaler, Antigene: Praktische Bedeutung für Diagnose und Nachsorge bei Malignomen, Therapiewoche, 28, 4081, 1978.(82) NØRGAARD-PEDERSEN B, Scand. J. Immunol., 5, Suppl. 4, 1, 1976.
(83) DATI F., GRENNER G., SCHMIDTBERGER R., Quantitation of alpha-fetoprotein (AFP) by enzyme-linked immunosorbent assay, J. Clin. Chem. Clin. Biochem., 19, 216, 1981.
MAIOLIN R., FERRUA B., MASSEYEFF R., J. Immunol. Meth., 6. 355, 1975.
LAMERZ R., FATEH-MOGHADAM A., ibidem
HEVEY R., SPARACIO R., PETKO W., BONACKER L.H., Measurement of Alpha1-Fetoprotein by Enzyme Immunoassay Using Peroxidase Labeled anti-Alpha1-Fetoprotein, Behring Inst. Mitt., 59, 102, 1976.
An exception should be made for AFP levels in the amniotic fluid, where pathological levels are more than 1000 times higher, and where less sensitive methods are quite satisfactory, such as radial immunodiffusion (LC-PARTIGEN® AFP, Hoechst), laser nephelometry, and turbidimetry.(84) CONCANNON J.P. et al., Cancer, 34, 184, 1974.
GROPP C., LEHMANN F.G., HAVEMANN K., Dtsch. med. Wschr., 102, 1079, 1977.
GROPP C., HAVEMANN K., LEHMANN F.G., Cancer, 42, 2802, 1978.
LAURENCE D.Jr., et al., Brit. Med. J., 111, 605, 1972.
LO GERFO P., KRUPEY J., HANSEN H.J., New Engl. J. Med., 285, 138, 1971.
VINCENT R.B., CHU T.M., J. tharac. cardiovas. Surg., 66, 320, 1973.(85) GROPP C., LUSTER W., Tumormarker beim Bronchialkarzinom : Parameter für Frühdiagnostik, Stadieneinteilung und Therapiekontrolle, Laboratoriumsblatter, 2, 49, 1982.
ELISA methods as well as RIA methods exist for CEA determination.
(86) Hoffman-Laroche, Abbot, Amersham Ltd. (GB) and Pharmacia Inc. of Piscataway N.J. (USA) have all requested FDA approval for AFP test kits.
(87) LÜTHGENS M., SCHLEGEL G., EKLUND G., and BJÖRKLUND B., Correlation between Activity in Breast Cancer and CEA, TPA and Eighteen Common Laboratory Procedures and the Improvement by the Combined Use of CEA and TPA, Tumor Diagnostik, 2, page 6-11 (1981)
(88) EKLUND G., BJÖRKLUND, B. and HERBERMAN, R., Evaluation of Tissue Polypeptide (TPA) and Carcinoembryonic Antigen (CEA) in a Coded Panel of Sera from Cancer Patients and Controls, 1981.
(89) LÜTHGENS M. et al. ibidem
(90) ANDREN-SANDBERG A. and ISACSON S., Tissue Polypeptide Antigen in Colorectal Carcinoma, in Clinical Application of Carcinoembryonic Antigen Assay, Excerpta Medica International Congress Series no. 439, pps. 139-143 (1977).
(91)
(92) HENNEBERRY M.O., ENGEL G.E. GRAYHACK J.T., Urol. Clin. North America, 6. 629, 1979.
CHOE B.K. et al., Cancer: Treat. Rep., 61, 201, 1977.(93) E.C. 3.1.3.2. is the International Union of Biochemistry's enzyme code.
(94) HENNEBERRY M.O. et al. ibidem.
ABUL-FADL M.A.M., KIND E.J., Biochem., J., 45, 51, 1949.
ROMANS N.A., ROSE N.R., TANNENBAUM M., Hum. Path., 10, 501, 1979.(95) GUTMAN A.B., GUTMAN E.B., An "acid" phosphatase occuring in the serum of patients with metastasizing carcinoma of the prostate gland., J. of Clin. Investigation, 17, 473, 1938.
(96) HENNEBERRY M.O., et al., ibidem.
YAN L.T., Amer. J. Med., 56, 604, 1974.(97) FISCHMAN W.H., LERNER F., A Method for estimating serum acid phosphatase of prostatic origin, J. of Biol. Chemistry, 200, 89, 1953.
(98) ibidem.
(99) SHULMAN S., MAMROD L., GONDOR M.J., SOANES W.A., The detection of prostatic acid phosphatase by antibody sections in gel diffusion, J. Immonol., 93, 474, 1964.
(100) ABLIN R.J., BRONSON P., SOANES W.A., WITEBSKY E., Tissue and species specific antigens of normal human prostatic tissue, J. Immunol., 104, 1329, 1970
(101) FOTI A.G., HERSCHMANN H.H., COOPER J.F., A solid phase radioimmunoassay for human prostatic acid phosphatase, Cancer Res., 35, 2446, 1975.
see also:
COOPER J.F., FOTI A.G., HERSCHMANN H.H., FINKLE W., A solid phase radioimmunoassay for prostatic acid phosphatase, J. Urol., 119, 388, 1978.
VIHKO P., SAJANTI, E., JANNE O., PELTONEN L., VIHKO R., Serum prostate-specific phosphatase. Development and validation of a specific radioimmunoassay, Clinical Chemistry, 24/11, 1915, 1978.(102) GRENNER G., Determination for prostatic acid phosphatase (PAP) by enzyme immunoassay, Clin Chem, 26, 987, 1980.
see also:
BAUER H.W., GÖTTINGER H., GRENNER G., DATI F., Enyme Immunoassay for prostate-specific acid phosphatase (E.C. 3.1.3.2.), Urol. Res., 9, 21, 1981.(103) CHOE B.K., ROSE N.R., KAROL M., PONTES E.J., Immunoenzyme assay for human prostate phosphatase, Proc. Soc. Exp. Biol. Med., 162, 396, 1979.
(104) GRENNER G., DATI F., in VOGT, W. (ed.), Radioactivitätsfreie, quantitative Immunoassays in der klinische Chemie, Stuttgart, New York, 51, 1981.
FOTI A.G., HERSCHMANN H.H., COOPER J.F., Clin. Chem. 23, 95, 1977.
JACOBI G.H., ERENTHAL W., ENGELMANN U., GRIMM D., RIEDMILLER H., PRELLWITZ W., HOHENFELLNER R., Immunologische Phosphatase Bestimmung beim Prostatkarzinom. II. Serumuntersuchungen mittels ELISA-Methode (ENZYGNOST (R) - PAP), Akt. Urol., 12, 283, 1981.(105) FOTI A.G., HERSCHMANN H.H., COOPER J.F., A solid phase radio-immunoassay for human prostatic phosphatase, Cancer Res., 35, 2446, 1975.
VIHKO P., et al. ibidem.
MAHAN D.E., DOCTOR B.P., Clin. Biochem., 12, 10, 1979.
GRENNER G., SCHMIDTBERGER R., Enzymeimmunologische Bestimmung der sauren Prostataphosphatase, J. Clin. Chem. Clin. Biochem., 17, 156, 1979.
CHOE B.K., et al. ibidem.
BAUER H.W., GÖTTINGER H., GRENNER G., Ein Enzymimmunoassay Zum Nachweis von prostatspezifischer saurer Phosphatase beim Prostatkarzinom, 31. Verhandlungsbericht der Dt. Gesellschaft für Urologie, Berlin-Heidelberg-New York, 470, 1980.(106) BAUER H.W., et al., Tumordiagnostik, 1, 44, 1981.
COOPER E.H. et al., Clin. Chim. Acta, 113, 27, 1981.
JACOBI, G.H. et al., Verhandlungsbericht der Dt. Gesellschaft für Urologie; Berlin-Heidelberg-New York, 109, 1981.
GRENNER G., DATI F., in VOGT, W. (ed.), op cit.(107) COOPER E.H., BAUER H.W., DATI F., Die immuno-chemische Bestimmung der sauren Prostata-Phosphatase (PAP) beim Prostata-Karzinom, Laboratoriumsblätter, 2, 87, 1982.
(108) JACOBI G.H., et al. ibidem.
(109) FLÜCHTER S.H., BICHLER K.H., HARZMANN R., 32. Verhdlber. der Dt. Ges. f. Urol., Berlin-Heidelberg-New York, 124, 1981.
(110) COOPER E.H., BAUER H.W., DATI F., op cit.
(111) OFFNER M., Interet clinique de la determination des phosphatases acides prostatiques par methode immuno-enzymatique, manuscript.
Of the 241 patients examined only four with a PAP level of more than 2.0 g per litre had no discernible cancer. However, three of the four later developed clinically observable prostate epithelioma.(112) JACOBI G.H., et al. ibidem.
(113) BAUER H.W., WALTHER V., SCHMIEDT, E. Fortschr. Med. 98, 1301, 1980.
Dr. Henri ROSENBERG, LL.D., Ph.D., N.D.
Doctor of Naturopathy
Permanent Member of the British
Guild of Drugless Practitioners.
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| Karl Loren Web | Vibrant Life Web | Karl Loren's Book | |
| Super Colostrum | Bulk MSM | Heart Disease | |
| Emmessar | Happiness | Arthritis | |
| Instead Of | Chelation Therapy | Super Colostrum (2) | |
| Karl Loren's Catalog Store | Central Page For All 12 Webs! | ||
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I promise to answer your message -- click here to send me a personal message
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SUBSCRIBE: The Wednesday Letter is a free electronic monthly newsletter written and published by Karl Loren. You can view more than 50 back issues of this publication by clicking here. The Wednesday Letter subscription list is maintained on a secure server, no name is ever given or sold to anyone, and it is never used except for this Newsletter. It is automatically published on the Tuesday night just before the first Wednesday of every month. You can subscribe to this free monthly electronic letter by entering your eMail address and name below. You will then automatically receive a request for confirmation, sent to whatever address you have entered. If you do NOT receive this confirmation request, then you will not be subscribed. There may have been an error with your address and you should resubmit. The letter is never sent twice to the same address -- so you do not have to worry about a duplicate subscription. When you receive this confirmation request you must reply to it, or your subscription will not become active. No one can subscribe your name, and address, without you being notified, and if you get an unwanted notice of subscription you only need to DO NOTHING and the subscription will NOT be active.
REMOVAL: You can remove yourself from the subscription list in several different ways. Click here to read about this entire newsletter system. Every edition of The Wednesday Letter is delivered to your address with YOUR name and address in view on the letter, with a link that allows you to remove THAT name from the subscription list. If you try to send this removal message from an address different from the one you used to send in your original confirmation, then you will get a warning notice first, sent to the subscription address, asking you to confirm that you want to be removed from the list -- by replying to THAT request for confirmation, you will then be automatically removed. Thus, no one else can unsubscribe you, from some other computer, without your knowledge. But, if you send in the unsubscribe notice from the same machine used to receive the Letter, then the removal from the subscription list is automatic.
Personal Message: When you send a personal message to Karl Loren, you will receive a personal reply as per his instructions. Karl pledges that every personal message will get a personal answer. When you provide your mail address, we will send you free information including our free catalog and a cassette tape lecture by Karl Loren about heart disease, no charge, by mail, even if outside the US. You can select particular information you would like to receive, along with the free cassette tape and catalog.
