concanavalin-a and Choriocarcinoma

The case is presented of a 46 year old woman who had a gastric tumor with components of choriocarcinoma, hepatoid adenocarcinoma and common types of adenocarcinoma. Although two histologic types of tumor producing carcinoplacental or carcinofetal proteins were contained within the tumor, immunohistochemical analyses, especially of placental alkaline phosphatase, clearly showed that each component was present separately within the same tumor. It was only hepatoid adenocarcinoma cells that permeated the lymph and blood vessels. After the recurrence, the serum level of alpha-fetoprotein (AFP) markedly elevated, but that of human chorionic gonadotropic beta-subunit (hCG-beta) was always within normal range. These findings indicate that in the present case the hepatoid adenocarcinoma component was more aggressive in growth than the choriocarcinoma component.

Topics: Adenocarcinoma; alpha-Fetoproteins; Choriocarcinoma; Concanavalin A; Female; Humans; Immunoenzyme Techniques; Middle Aged; Neoplasms, Multiple Primary; Stomach Neoplasms

This study investigates the physicochemical characteristics of human chorionic gonadotropin (hCG) in gestational trophoblastic disease (GTD), with special reference to the clinical course of chemotherapy and prognosis. In gel high performance liquid chromatography (HPLC), the hCG molecules from normal pregnancy and from the hydatidiform mole had the same molecular form as standard purified hCG, whereas hCG from choriocarcinoma was inconsistent in molecular form, containing molecules which are smaller, the same or larger than those of standard purified hCG. In two fatal choriocarcinoma patients, large hCG and large hCG alpha were found in the urine samples collected within one month prior to death. In a chromatofocusing study, the chromatofocusing pattern of hCG from GTD was acidic and similar to that of early pregnancy. The chromatofocusing patterns did not alter or were altered only slightly during the course of chemotherapy. In a Concanavalin A-Sepharose (Con A) chromatography study, the Con A binding shifted from low to high binding in patients with GTD who were responsive to chemotherapy. In summary, the molecular form, electric charge and Con A binding of hydatidiform mole hCG are similar to those of early pregnancy hCG and standard purified hCG, whereas the molecular form and Con A binding of choriocarcinoma are different from those of early pregnancy hCG and standard purified hCG. The presence of smaller or larger molecular forms of hCG may be an ominous sign, whereas the presence of high Con A binding may be a favorable sign. The chromatofocusing pattern seems to be unrelated to the clinical course of chemotherapy.

Topics: Choriocarcinoma; Chorionic Gonadotropin; Chromatography, Agarose; Chromatography, High Pressure Liquid; Concanavalin A; Female; Glycopeptides; Glycosylation; Humans; Hydatidiform Mole; Isoelectric Focusing; Pre-Eclampsia; Pregnancy; Prognosis; Trophoblastic Neoplasms; Uterine Neoplasms

The effect of TBG on the functional activity of different cell lines, spontaneous and Con A induced proliferation of PBL was studied. If concentration of TBG is higher than 50 mu kg/ml it suppresses the proliferation in many used cell lines, except choriocarcinoma and cancer of uterus. The reliable increasing of spontaneous proliferation of PBL, Jurkat and K-562 cells may be observed if concentration is more lower (0.5-15 mu kg/ml). However proliferation of other cell lines corresponds to control level, and Con A induced proliferation of PBL is inhibited. The effect was more marked at 48, as compared to 24 hours of cell incubation with TBG.

Topics: Biomarkers, Tumor; Cell Division; Cell Line; Choriocarcinoma; Concanavalin A; Female; HeLa Cells; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Leukemia, T-Cell; Lymphocytes; Lymphoma, B-Cell; Lymphoma, T-Cell; Pregnancy-Specific beta 1-Glycoproteins; Tumor Cells, Cultured; Uterine Neoplasms

We have investigated the functional ability of a choriocarcinoma-cell-derived factor to block human T cell responses and the factor's immunoregulatory site of action on the T cell signal transduction pathway. The factor completely suppressed human T cell responses activated by phorbol ester and calcium ionophore, reagents which strongly stimulate IL-2-mediated T cell responses. It failed to inhibit CD 25 expression and IL-2 production by T cell blasts in the T cell activation phase, but completely blocked recombinant IL-2-induced proliferation of T cell blasts in the T cell proliferation phase. Absorption experiments with the factor and Con A-induced T cell blasts as well as [125I]IL-2 binding experiments with T cell blasts revealed that the factor acted on the physiological events occurring after IL-2-mediated stimulation of IL-2 receptor complexes, demonstrating no interaction of the factor with either IL-2 molecules or IL-2 receptor complexes. Moreover, it suppressed murine IL-2 dependent T cell line proliferation, suggesting the presence of common pathways in human and murine T cell proliferation. The biological and immunological significance of the factor during pregnancy and in the immunosuppressed tumor-bearing hosts are discussed.

Topics: Calcimycin; Cell Differentiation; Cell Division; Choriocarcinoma; Concanavalin A; Humans; Immune Tolerance; Interleukin-2; Receptors, Interleukin-2; Recombinant Proteins; Suppressor Factors, Immunologic; T-Lymphocytes; Tetradecanoylphorbol Acetate; Trophoblasts; Tumor Cells, Cultured

A light microscopic analysis of lectin receptors in normal placenta and trophoblastic disease was performed utilizing biotinylated Concanavalin-A (Con-A), wheat germ agglutinin (WGA), and peanut agglutinin (PNA), in conjunction with an avidin-biotin peroxidase complex. Hydatidiform mole, invasive mole and choriocarcinoma exhibited increased receptors to Con-A and WGA compared to normal placenta. Increased reactivity to Con-A and WGA was associated merely with increased growth and proliferation of trophoblasts rather than a malignant transformation. Normal placenta, partial and complete mole generally showed moderate to strong binding with PNA after neuraminidase treatment, while invasive mole and choriocarcinoma (11 of 15 cases) generally showed minimal to absent reaction with PNA. Heterogeneity of PNA binding in choriocarcinoma was manifested by the presence of PNA reactivity in the trophoblast membrane in 2 cases wherein no prior neuraminidase treatment was given. This suggests that in some malignant trophoblasts, there is absence of sialic acid in the terminal cell surface carbohydrate groups resulting in the exposure of N-acetylgalactoseamine.

Topics: Choriocarcinoma; Concanavalin A; Female; Humans; Hydatidiform Mole; Hydatidiform Mole, Invasive; Lectins; Monosaccharides; Peanut Agglutinin; Placenta; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms; Wheat Germ Agglutinins

Supernatants from activated leukocyte cultures and individual lymphokines and monokines were added to cultures of JEG-3 human gestational choriocarcinoma cells in vitro, and effects on cell proliferation were measured. Activated leukocyte culture supernatants, recombinant gamma-interferon, tumor necrosis factor, and colony-stimulating factor significantly inhibited JEG-3 proliferation. In contrast, high doses of both interleukin 1 and 2 stimulated JEG-3 proliferation. Low doses of B cell growth factor stimulated JEG-3 proliferation, whereas the highest dose was inhibitory. Further understanding of the effects of lymphokines and monokines on trophoblastic growth may provide important insights into immunologic mechanisms affecting early pregnancy development and tumor-host interactions in gestational trophoblastic neoplasia.

Topics: Biological Products; Cell Division; Cell Line; Choriocarcinoma; Colony-Stimulating Factors; Concanavalin A; Female; Humans; Interferons; Interleukin-4; Interleukins; Lymphocyte Culture Test, Mixed; Lymphokines; Monokines; Tumor Necrosis Factor-alpha; Uterine Neoplasms

We have observed low-molecular weight carboxyterminal fragments of the human choriogonadotropin (hCG) beta-subunit in the urines of several women with choriocarcinoma, and we have characterized one fragment in detail. Its apparent molecular weight by gel chromatography on Sephadex G-100 was 14,200. The fragment was not adsorbed to concanavalin A-Sepharose, indicating that it lacked the asparagine-linked carbohydrate groups of intact hCG beta. It was active in radioimmunoassays (RIA) using antisera either to the hCG beta carboxyterminal peptide (CTP) or to the desialylated hCG beta CTP (hCG beta as-CTP), indicating the presence of not only the hCG beta carboxyterminus but also desialylated O-serine-linked carbohydrate side chains on the fragment. It lacked luteinizing hormone/choriogonadotropin radioreceptor activity and hCG beta conformational immunoreactivity (SB6 RIA). On Sephadex G-100 gel chromatography, the elution profiles of this fragment and the hCG beta as-CTP(115-145) prepared by trypsin digestion of as-hCG were essentially indistinguishable (apparent molecular weights 14,200 and 14,000, respectively). The immunological characteristics of the fragment in both hCG beta CTP and hCG beta as-CTP RIA were indistinguishable from those of the hCG beta as-CTP(115-145) glycopeptide. Carboxyterminal fragments of hCG beta were evident in urine specimens obtained from 10 of 11 patients with choriocarcinoma but not in those obtained from normal subjects who were given an intravenous infusion of highly purified hCG. Of six pregnant women, only the one at term excreted carboxyterminal fragments of hCG beta and then only in trace amounts. We conclude that hCG beta carboxyterminal fragments, including one that is indistinguishable from the tryptic glycopeptide hCG beta as-CTP(115-145), can occur naturally in the urine of patients with choriocarcinoma.

Topics: Choriocarcinoma; Chorionic Gonadotropin; Chromatography, Gel; Concanavalin A; Epitopes; Female; Humans; Molecular Weight; Peptide Fragments; Pregnancy; Protein Binding

The binding of pregnancy-specific beta-1-glycoprotein (SP1) to Concanavalin A (Con A) has been studied in serum samples from 34 pregnant women and 13 patients with trophoblastic diseases. In normal pregnancy and in hydatidiform moles, the fraction that did not bind to Con A accounted for 0.5--4.3% of the total SP1 concentration whereas, in 5 out of 6 patients with choriocarcinoma, the fraction was 4.8--30%. The secretion of Con A non-binding SP1 appears to be an inherent characteristic of some malignant trophoblast tissues and may result from its altered glycosylation.

Topics: Choriocarcinoma; Concanavalin A; Female; Humans; Pregnancy; Pregnancy Proteins; Pregnancy Trimester, First; Pregnancy Trimester, Third; Pregnancy-Specific beta 1-Glycoproteins; Trophoblastic Neoplasms; Uterine Neoplasms

The cultured human choriocarcinoma JEG-3 cells secrete biologically active HCG and free HCG alpha-subunit. When compared with the alpha-subunit dissociated from HCG obtained either from pregnancy urine or JEG-3 cells, free alpha-subunit has a larger molecular weight, is more acidic and is non-functional, lacking the property to recombine with the HCG beta-subunit. The understanding of the biochemical differences observed between free alpha-subunit and alpha-subunit found in HCG is important and should help to unravel the biosynthesis of gonadotrophins. Two proteins which bind to the cell membrane, epidermal growth factor and concanavalin A, are capable of stimulating JEG-3 cell secretion. Epidermal growth factor stimulates the secretion of HCG while concanavalin A stimulates both HCG and HCG alpha-subunit secretion. Amphotericin B, an antifungal agent commonly used in tissue cultures, which also affects the cell membrane, was shown to stimulate HCG and HCG alpha-subunit secretions. The use of these agents should contribute to the understanding of membrane-related events which lead to the secretion of HCG and alpha-subunit.

Topics: Amphotericin B; Cells, Cultured; Choriocarcinoma; Chorionic Gonadotropin; Concanavalin A; Epidermal Growth Factor; Female; Humans; Pregnancy; Uterine Neoplasms

The cellular origin and target specificity of two types of soluble mediators viz., the inhibitor of DNA synthesis (IDS) and the stimulator of DNA synthesis (SDS) have been studied. These mediators were produced by human and murine lymphocytes derived from different organs and stimulated by different mitogens, viz. phytohaemagglutinin (PHA-P), concanavalin A (Con A) and lipopolysaccharide (LPS). Their target effect was quantitated by assessing the 3H-thymidine incorporation of murine and human lymphocytes stimulated by different T and B cell mitogens (Con A, PHA and LPS). IDS activity was detected in supernatants of PHA stimulated lymphocytes originated from immunologically hyporeactive patients (tumor-bearing patients, pregnant women) in contrast to majority of control patients. Marked "SDS" activity was produced by normal lymphocytes as tested in human and murine lymphocytes stimulated by Con A or PHA, while IDS activity was detected if the target cells were stimulated by LPS. The effects of "SDS" failed to show species specificity using human and murine test-systems.

Topics: Adult; Animals; Breast Neoplasms; Cells, Cultured; Choriocarcinoma; Concanavalin A; DNA; Female; Humans; Lipopolysaccharides; Lymphocyte Activation; Lymphocytes; Male; Mice; Mice, Nude; Phytohemagglutinins; Pregnancy; Species Specificity; Uterine Neoplasms

Topics: Cell Line; Choriocarcinoma; Chorionic Gonadotropin; Concanavalin A; Female; Humans; Kinetics; Methylmannosides; Peptide Fragments; Pregnancy