concanavalin-a and Uterine-Neoplasms

Endocervical and endometrial tissues were stained with four lectins to determine the difference in staining pattern between non-neoplastic and neoplastic conditions of these tissues.. The lectins used were Ulex europaeus agglutinin (UEA), Dolicho biflorus agglutinin (DBA). Concanavalin A (Con A), and Phaseolus vulgaris agglutinin (PHA). Endocervical tissues included normal endocervical glands, microglandular hyperplasia, minimal deviation adenocarcinoma and endocervical adenocarcinoma, well to poorly differentiated types. Endometrial tissues were collected from normal endometrium, simple glandular hyperplasia, complex hyperplasia, atypical hyperplasia and adenocarcinoma grades 1-3. Non-neoplastic and neoplastic endocervical and endometrial glandular epithelium showed positive reaction for UEA, Con A and PHA. Non-neoplastic glands showed mild to moderate intensity and apical and/polar type of staining pattern for all lectins. Endocervical adenocarcinoma including minimal deviation adenocarcinoma (MDC) and adenocarcinoma well to moderately differentiated type showed diffuse cytoplasmic type of staining pattern for all lectins, but poorly differentiated adenocarcinoma of endocervix showed only a stromal pattern for all lectins. Endometrial hyperplasia and adenocarcinoma grades 1-3 showed positive reaction for all lectins except for DBA. The staining pattern of endometrial hyperplasia was variable, but adenocarcinoma grades 1-3 showed diffuse type.. Intensity and staining patterns of lectins are helpful in distinguishing between endocervical and endometrial non-neoplastic and neoplastic lesions. Intense positive reaction of MDC, especially for Con A and PHA, can differentiate this lesion from normal endocervical glands. The stromal type of staining pattern of poorly differentiated endocervical adenocarcinoma can also have diagnostic significance. Negative reactions of DBA lectin for endometrial adenocarcinoma can be used for differentiating it from endocervical adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Cervix Uteri; Concanavalin A; Diagnosis, Differential; Endometrium; Epithelium; Female; Humans; Hyperplasia; Lectins; Middle Aged; Phytohemagglutinins; Plant Lectins; Staining and Labeling; Uterine Cervical Neoplasms; Uterine Neoplasms

Human chorionic gonadotropin (hCG) is a glycoprotein of which sugar chains are considered to show structural changes with malignancy. To study the sugar chain heterogeneity of urinary hCG in patients with gynecological disease, we employed serial lectin affinity chromatography (LAC) using concanavalin A (Con A) and phytohemagglutinin-E (PHA-E) which can separate N-glycoside-linked sugar chains, and Jacalin lectin which is specific for O-glycoside-linked sugar chains. The proportion of hCG which did not bind to Con A was clearly higher in patients with cervical cancer than in healthy pregnant women. The complex-type sugar chains bearing bisecting (beta 1-4) N-acetylglucosamine which bound to PHA-E increased in the early stage of cervical cancer, and tri- and tetra-antennary complex type sugar chains also increased in the advanced stages. In addition, the Jacalin-bound hCG increased significantly along with the stage of the cancer, especially in advanced cervical cancer with distant metastases. Taken together, these results show that alteration in sugar chain structures of hCG reflect the advanced stage of cervical cancer.

Topics: Carbohydrates; Chorionic Gonadotropin; Chromatography, Affinity; Concanavalin A; Diagnosis, Differential; Endometriosis; Female; Humans; Phytohemagglutinins; Pregnancy; Uterine Cervical Neoplasms; Uterine 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

In a previous study we showed that endometrial carcinoma (EC) patients have a T cell deficiency manifested in a reduced ability to be stimulated in vitro by PHA and to produce IL-2. In an attempt to understand the mechanism responsible for this alteration we present in this paper a study on T cells characterized by the ability to form rosettes, with human erythrocytes, following Con-A activation (designated auto-rosette forming cells--ARFC). These cells are also known to manifest suppressive activity. We show that the frequency of ARFC in con-A activated peripheral blood leukocytes (PBMC) of EC patients is significantly (2-5 fold) higher than that of healthy age-matched controls or that of patients with stage--I colon or vaginal cancer. Endometrial carcinoma is known to be associated with long term exposure to estrogens unopposed by progestins. Examining the possible role of estrogens in increasing the frequency of ARFC from EC patients, we found that in vitro addition of estradiol to Con-A stimulated PBMC from healthy donors increased the frequency of ARFC to levels found in EC patients. Tamoxifen, an anti estrogen drug, reduced the frequency of the estrogen stimulated ARFC to the original low level. Our results suggest a dual role for estrogen in carcinogenesis as well as in immunomodulation.

Topics: Concanavalin A; Endometrial Hyperplasia; Estradiol; Estrogens; Female; Humans; In Vitro Techniques; Lymphocyte Activation; Middle Aged; Rosette Formation; T-Lymphocytes; Tamoxifen; 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

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

The effects of peripheral mononuclear cells on the production of TA-4 were studied using SKG-IIIa cells, an established cell line of squamous cell carcinoma. The mononuclear cells were isolated from the heparinized peripheral blood from healthy donors and patients with uterine cancer, and were treated with Con A for 3 days. The supernatant of Con A treated mononuclear cells significantly increased TA-4 release from SKG-IIIa cells, but also induced apparent cytotoxicity. The cellular TA-4 content, which was determined by the specific RIA or by immunohistochemical staining using TA-4 antibodies, was also increased by the treatment. There was significant difference in stimulating activity from the mononuclear cells in healthy donors and malignant patients. These stimulating factors from the mononuclear cells had molecular weights of 36,000, 61,000 or 82,000 daltons on Sephadex G-100 column chromatography, whereas the cytotoxic activity was eluted in those fractions with molecular weight of 61,000 daltons. These results indicated that the production of TA-4 in squamous cell carcinoma could be stimulated by some factors from the peripheral mononuclear cells.

Topics: Antigens, Neoplasm; Biological Factors; Carcinoma, Squamous Cell; Concanavalin A; Cytotoxicity, Immunologic; Female; HeLa Cells; Humans; Immunohistochemistry; Isoelectric Focusing; Leukocytes, Mononuclear; Male; Molecular Weight; Tumor Cells, Cultured; Uterine Neoplasms

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

The effect of surgery on peripheral blood mononuclear cell responsiveness to mitogens and suppressor cell (SC) activity assessed in a concanavalin A (ConA) assay were studied in patients with stage 0 and stage III-IV cancer. Patients were exposed to a similar surgical trauma the same type of anaesthesia, and to no pre- and early postoperative radio- or chemotherapy. A more pronounced postoperative decrease in the lymphocyte count, responsiveness to phytohemagglutinin (PHA) and ConA, and in the SC activity was found in the nonadvanced than advanced cancer group. These findings point to an impaired mobilization and distribution capacity of circulating lymphocytes in patients with advanced neoplastic disease.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Cells, Cultured; Colonic Neoplasms; Concanavalin A; Female; Humans; Leukocyte Count; Leukocytes, Mononuclear; Lymphatic Metastasis; Lymphocytes; Middle Aged; Neoplasm Metastasis; Phytohemagglutinins; Stomach Neoplasms; T-Lymphocytes, Regulatory; Uterine Neoplasms

Topics: Agglutination; Concanavalin A; Female; Humans; Liposomes; Membrane Fluidity; Membrane Lipids; Uterine Neoplasms; Uterus

The effect of surgery on suppressor cell (SC) activity assessed in a ConA assay and concentration of OKT8+ cells in peripheral blood were studied in 16 patients with stage 0 cancer of uterus. An evident decrease in the number of freshly obtained OKT8+ and cultured for 20 hr with ConA OKT8+ cells and subsequently a drop in whole blood suppressor activity were found in the immediate postoperative period. The recovery of SC activity but not of OKT8+ cell level was observed on day 5. A nonsignificant decrease in E-RFC suppressor activity compared with that of whole blood SC suggests that function of T-suppressors has not been affected. The non-T cells did not produce any suppressive effect. These results indicate that the postoperative drop in the blood SC activity is due to the temporary depletion and not to the depressed function of SC.

Topics: Adult; Aged; Antibodies, Monoclonal; Concanavalin A; Female; Humans; Leukocyte Count; Middle Aged; Surgical Procedures, Operative; T-Lymphocytes, Regulatory; Uterine Neoplasms

The influence of operative trauma on the responsiveness of PBM to PHA and Con A and the level of Con A-induced suppressor cell (Con A-SC) activity toward autologous responder cells (RC) were examined in patients with stage 0 uterine cancer after hysterectomy. The operation brought about a decrease on the second post-operative day in the responsiveness of PBM to various concentrations of PHA by 19.2-28.8% and to Con A by 31.2-41.8%, concomitantly with a decline in Con A-SC activity from 43.7 to 22.0%. When the Con A-SC were tested against RC obtained from blood samples drawn prior to surgery and stored at -196 degrees C, an increase in the post-operative SC activity from 41.6 to 52.2% was observed which might indicate a post-operative stimulation of SC. On the other hand, when Con A-SC were raised from PBM drawn before surgery and tested against RC obtained post-operatively, they displayed a decreasing suppressive activity from 27.2 to 2.7%. This might be due to the pre- and post-operative stimulation of RC. The observed changes were most likely caused by a transient decrease in the number of blood T lymphocytes, altered proportions of blood T cells to other PBM cells and probably a non-specific stimulation of autologous cells responding in the suppressor cell activity assay.

Topics: Adult; Aged; Concanavalin A; Female; Humans; Hysterectomy; Leukocyte Count; Lymphocyte Activation; Middle Aged; Phytohemagglutinins; T-Lymphocytes, Regulatory; Uterine Neoplasms

We further studied the androgen-binding protein (ABP) that we recently evidenced in the serum from two patients with hydatidiform mole [Ref. 4]. This protein was further shown to be distinct from the sex hormone-binding globulin (SHBG) by concanavalin A and ion-exchange chromatographies, as well as spectrophotometric and kinetic studies. However, the ABP was shown to have a molecular weight and relative affinities for several steroids, similar to those of SHBG. Our results lead us to suppose that the ABP previously evidenced in molar vesicles and fluid [Ref. 5] is secreted in the serum. It is, however, likely that the secretion process alters the binding affinity of this protein. The presence of this additional binding component in the serum of patients with such trophoblastic tumours, may reduce severely the free 17 beta-hydroxyandrogens levels, as well as may help create a release gradient in the serum steroids buffer stores.

Topics: Androgen-Binding Protein; Carrier Proteins; Chromatography; Concanavalin A; Dihydrotestosterone; Female; Gonadal Steroid Hormones; Humans; Hydatidiform Mole; Pregnancy; Progesterone; Sex Hormone-Binding Globulin; Spectrophotometry; Uterine Neoplasms

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