Casein and breast cancer.
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Biomedical subjects
Publications and source records attributed to J C Hendrick.
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Extracts of various organs, mammary tumours and sera from milk-borne MMTV infected Swiss albino mice of different age, sex and physiological conditions were tested by radioimmunoassay for the presence of gp47, the main envelope polypeptide, and p28, the main core protein of the virus. Except in brain, ovaries and testes, both antigens were found in all organs of old animals and of females after the onset of their first pregnancy. Antigens were not present in organs of weanlings or in whole foetuses. Higher values were found in mammary glands, mammary tumours, epididymis and seminal vesicles. These organs also harboured a greater amount of gp47 than p28. The serum generally contained gp47 but rarely p28. This indicates that gp47 is not virion-bound in blood. Pregnancy, lactation and especially the presence of mammary tumours increased the concentration of gp47 in serum. The results do not allow localization of target organs of MMTV infection in the interval between ingestion of the virus by the suckling mouse and the first pregnancy. Moreover, results obtained with one group of mice devoid of exogenous virus show that, as endogenous MMTV genome expresses p28, it might account for part of the p28 detected exogenous MMTV-infected mice.
The specificity of the gonadotropin short-loop feedback mechanism was investigated in castrated rabbits by blood sampling from an indwelling jugular venous catheter for follicle-stimulating hormone (FSH) after the intravenous administration of purified human luteinizing hormone (hLH). Although we have previously shown that such hLH administration results in a decrease of rabbit LH, no decrease in rabbit FSH was seen in these experiments. This specificity of LH feedback is compatible with the site of feedback being at the (1) pituitary level or (2) at the hypothalamic level provided two separate LH and FSH releasing factors exist.
Male domestic ducklings were injected during their first month of life with mammalian gonadotrophins (ovine LH or FSH, HMG) or gonadal steroids (testosterone or oestradiol). LH and testosterone stimulated sexual behaviour while oestradiol inhibited the increase of aggression observed in control birds during the experiment. The mammalian gonadotrophins did not increase plasma testosterone but nevertheless they all stimulated the testis growth. Several hypotheses which could explain this finding (stimulation of spermatogenesis without any apparent effect on testosterone) are discussed and the possibility of a direct action of LH on the sexual behaviour is analysed. Social displays were only moderately stimulated by testosterone and not at all by gonadotrophins. The hormonal controls of these behaviour patterns remains thus largely unknown.
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Five tumor markers can be simultaneously determined in the serum by radioimmunoassay: carcinoembryonal antigen (CEA), alpha-fetoprotein (alpha-FP), human chorionic gonadotropin (HCG), beta-subunit of HCG (beta-HCG) and kappa-casein. In a series of 935 healthy subjects, these antigens remain detectable or are detected within very precise limits. At the start of the clinical evolution of breast cancer, the incidence of pathological concentrations is increased as compared with the highest level observed in normal subjects. This high incidence is mainly due to a concomitant determination of CEA, kappa-casein, HCG and beta-HCG. The alpha-FP test is never positive, while the kappa-casein concentration is particularly high in the first clinical stages of breast cancer and with metastases. The concomitant determination of these tumor markers may be a biological element contributing to the diagnosis of neoplasia, although it is neither an absolute nor a specific criterium. Indeed, a pathological concentration of at least one antigen was observed in 5.5% of the subjects presenting with benign mastopathy. When metastases occur (25 patients), the incidence of pathological concentrations of at least one antigen increases: 88%, the absolute values of these levels increasing simultaneously. The determination of the antigen concentration therefore allows an evaluation of the extension of the disease. Surgical removal reduces the incidence of positivity of these antigens to 34%. Persistence of pathological levels seems to be related to a possibility of relapse or metastatic spreading. Finally, chemotherapy and radiotherapy applied on a tumor which is not excised, does not decrease the incidence of positivity of the tumoral markers, although their levels seem to fluctuate with the clinical evolution.
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The main protein of the core of murine mammary tumor virus, with a molecular weight of 28,000 (p28), was solubilized by deoxycholate treatment of the virus and purified by Ultrogel ACA-54 filtration and hydroxyapatite chromatography. This protein was used as labeled antigen in a highly specific and reproducible radioimmunoassay. Organ extracts of uninfected C57BL mice did not contain p28, but organ extracts of infected RIII mice did contain the antigen. Despite the high content in the mammary gland, the level of p28 in the other organs was identical in male and female mice. Sera of uninfected mice and the majority of the sera of infected mice did not contain the antigen. The investigation included 338 human sera (50, normal; 157, breast cancer; 77, polycystic disease; 32, benign mastopathy; 12, fibroadenoma; 10, at risk of developing breast cancer). None contained an antigen related to p28. Eight of 24 extracts of human breast cancer gave results that appeared weakly positive, possibly as a result of proteolysis. Extracts of healthy breast tissue and the serum from the breast arterial and venous blood of corresponding patients were negative.
Various technics of coupling (carbodiimide, glutaraldehyde, periodate) have been used for the grafting of human casein on glucose oxidase. The various types of product obtained were identified by gel filtration and used for drawing up titration curves. The authors compared radioimmunoassay and enzymoimmunologic estimation showing the importance of the molecular size of the conjugates obtained.
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Explore the source record for details and available documents.
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Five tumor markers were measured simultaneously in serum by radioimmunoassay: carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), human chorionic gonadotrophin (HGC), the beta subunit of HCG, and Kappa casein. In a population of 935 normal subjects these antigens were undetectable or found within precise limits. In patients with tumors of various origins the rate of pathologically elevated levels was 72% at the beginning of the clinical course (194 cases). This high rate was primarily due to the simultaneous measurement of CEA, betaHCG, HCG, and casein. AFP was of little importance. The simultaneous measurement of these tumor markers may be one biochemical element of diagnosis of carcinoma, although this criterion is neither absolute nor specific, as 14.7% of patients with non-neoplastic disorders (234 cases) were positive for one antigen. In the presence of metastases (112 cases) the rate of pathologic levels of at least one antigen was increased: 86% due to CEA and casein assay at the same time as their absolute levels were increased. Surgical removal reduces the rate of positivity of these antigens to 37%. As was shown in patients with breast cancer, the rate was 10% when the tumor had been removed at Stage N- and 54% when it was removed at Stage N+. Thus, the persistence of pathologic levels could be correlated with the capacity for recurrence or metastases. Finally chemotherapy, radiotherapy, or both, do not decrease the rate of positivity of the tumor markers.
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