Preoperative Sera Research Articles

Impaired Formation of the Ternary Insulin-Like Growth Factor-Binding Protein Complex in Patients with Hypoglycemia due to Nonislet Cell Tumors*

In some subjects with hypoglycemia associated with tumors of mesenchymal origin, high insulin-like growth factor-II (IGF-II) levels have been described in serum and in the tumors. Tumor IGF-II of 10-15 kDa circulates in a 60-kDa complex, in contrast to the ternary 150-kDa complex in which serum IGFs normally circulate together with the IGF-binding subunit (IGFBP-3) and the acid-labile subunit (alpha-subunit). This study examines the molecular distribution and complex-forming activity of the components of the ternary complex in the serum of subjects with mesenchymal tumor hypoglycemia. Total serum IGFBP-3 levels were 60% of normal in tumor patients and appeared at 60 kDa on gel chromatography, shifting after tumor removal to 150 kDa. Total alpha-subunit levels were 40% of normal in patients with tumors, increasing after tumor removal to 70% of normal and changing in elution profile from a peak typical of uncomplexed alpha-subunit to the normal broad peak representing both complexed and uncomplexed alpha-subunit. Although low by RIA, alpha-subunit activity in a ternary complex formation assay was normal, indicating that the ability of free alpha-subunit in the patients' circulation to combine with exogenous IGFBP-3 plus IGF-I was not impaired. In contrast, in an assay that tested the ability of IGF-IGFBP complexes in the patients' circulation to combine with pure alpha-subunit, complex formation activity was 75-85% below normal in preoperative sera, despite low normal IGFBP-3 levels. Therefore, the cause of hypoglycemia in these patients may be the inability of complexes between the abnormal tumor IGF-II and IGFBP-3 to be sequestered in the biologically inactive ternary complex.

Detection of gangliotriaose-series glycosphingolipids in serum of cord blood and patients with neuroblastoma by a sensitive TLC/enzyme-immunostaining method

Concentration of gangliotriaose-series glycosphingolipids, including G A2, G M2, G D2 and G T2, was measured in human sera by a thin-layer chromatography/enzyme-immunostaining method. By this method, as little as 5–10 ng/ml of these glycolipids in serum could be determined simultaneously. Although G D2 ganglioside could be consistently detected in normal cord blood (1–2 ng/ml of serum), the ganglioside was never detected in normal adult serum. However, the same ganglioside was found to be present in large quantity in preoperative sera of 6/9 patients with neuroblastomas (25–658 ng/ml of serum). In addition to G D2 gangliosides G M2 and G M2 increased concomitantly than usual. It is concluded that this highly sensitive quantification of the tumor-associated glycolipids circulating in serum of neuroblastoma patients could be useful in their diagnosis.

A preoperative chymopapain sensitivity test for chemonucleolysis candidates.

A fluorescence enzyme immunoassay (ChymoFAST test) for the quantitation of chymopapain-specific IgE antibody concentration in human serum is described. The IgE antibody is recognized as the major immunologic mediator for anaphylactic reactions. Serum chymopapain-specific IgE levels serve as an objective screening method for identifying patients most likely to tolerate chymopapain, thereby minimizing associated risks. Preoperative sera obtained from 11,658 chemonucleolysis candidates were tested, of which 0.94% (110/11,658) were found to be positive. Good predictive values for both positive and negative findings are evident based on 4776 postmarketing surveillances obtained from the surgeons.

Stage-related correlations between immunoglobulins and complement components in preoperative sera from patients with gastric carcinoma

Immunoglobulins A, G and M and complement components C3, C4 and C1-INH were quantitated in sera taken preoperatively from 168 patients with gastric carcinoma. The values were grouped according to stages (pTNM). The concentrations of C4 and C1-INH increased with advancing stage of disease and were above normal mean values in all stages. The concentration of IgG was below the normal mean value among all the patients and with the lowest concentration in stage III. Concentrations of IgA and C3 were above normal means but without significant relation to stages. There was a positive correlation between the concentrations of IgG and C1-INH in sera from patients with stage IV carcinoma, while the same correlation was negative in stages I-III. Although the results varied among the patients within each stage, the profiles of immunoglobulin and complement concentrations are of value in the preoperative staging of the disease.

Serological evaluation of human brain tumors using a microradioisotopic staphylococcal protein a assay

A microradioisotopic staphylococcal protein A assay was applied to the serological evaluation of preoperative sera from brain tumor patients. The assay was performed in Terasaki plates, and a stainless steel punch and multiholed die facilitated sample prearation. Using allogeneic astrocytoma target cells, 15/19 of the brain tumor patients' sera were reactive, compared to 1/21 controls 0/7 nonmalignant brain disease patients' sera were positive, and 5/20 sera from patients with epithelial malignancies. The brain tumor sera were not reactive against a rectal cancer cell line.

Elevated activity of cytidine 5′-monophospho-N-acetylneuraminic acid hydrolase in serum of ovarian cancer patients as a possible indicator of malignancy

Cytidine 5′-monophospho-N-acetylneuraminic acid hydrolase activity has been demonstrated in homogenates of normal ovary and ovarian epithelial adenocarcinomas, as well as in the sera of normal individuals and ovarian cancer patients. The specific activity of the enzyme in ovarian tumors is significantly reduced compared to normal ovaries. In pre-operative sera of these patients, the activity is elevated about 2 fold in comparison with age and blood group matched controls. The patients with lower tissue enzyme activity have higher serum values. After tumor reductive surgery, serum levels of this enzyme are diminished, but are still higher than controls. Clinical use of this assay for detection and management of ovarian neoplasia is promising.

Measurement of Serum Ferritin by Radioimmunoassay: Results in Normal Individuals and Patients With Breast Cancer 2

Ferritins are iron-containing proteins found in normal tissues; they increase in concentration in many tumors and the blood of tumor-bearing individuals. We utilized a double-antibody radioimmunoassay for measurement of serum ferritin and defined the upper limit of normal as 146 ng/ml for women (mean 34 ng/ml) and 193 ng/ml for men (mean 93 ng/ml). Serum ferritin levels exceeded these limits in preoperative sera of 41% of women with mammary carcinoma (mean 199 ng/ml) and in 67% of women with locally recurrent or metastatic mammary carcinoma (mean 671 ng/ml). Individuals with hepatic inflammatory states are known to have high serum ferritin, and ferritin was increased in 43% of patients with hepatitis or cirrhosis (mean 364 ng/ml) and in 13% of patients with ulcerative colitis or gastroduodenal ulcers (mean 106 ng/ml). Measurement of serum ferritin may be useful in evaluation of patients with breast cancer and in monitoring their response to therapy.