concanavalin-a and Urinary-Bladder-Neoplasms

Intravesical instillation of chemotherapeutic drugs such as epirubicin (EPI) is routinely used to prevent tumor recurrence and progression after transurethral resection of bladder tumor. However, the lack of tumor selectivity often causes severe damage to normal bladder urothelium leading to intolerable side effects. Here, we analyzed abnormal changes in glycosylation in bladder cancer and identified mannose as the most aberrantly expressed glycan on the surface of bladder cancer cell lines and human bladder tumor tissues. We then constructed a lectin-drug conjugate by linking concanavalin A (ConA) - a lectin that specifically binds to mannose, with EPI through a pH-sensitive linker. This ConA-EPI conjugate conferred EPI with mannose-targeting ability and selectively internalized cancer cells in vitro. This conjugate showed selective cytotoxicity to cancer cells in vitro and better antitumor activity in an orthotopic mouse model of bladder cancer. Our lectin-drug conjugation strategy makes targeted intravesical chemotherapy of bladder cancer possible.

Topics: Administration, Intravesical; Animals; Antibiotics, Antineoplastic; Concanavalin A; Epirubicin; Humans; Mannose; Mice; Urinary Bladder Neoplasms

Combinations of cellular immune-based therapies with chemotherapy and other antitumour agents may be of significant clinical benefit in the treatment of many forms of cancer. Gamma delta (gammadelta) T cells are of particular interest for use in such combined therapies due to their potent antitumour cytotoxicity and relative ease of generation in vitro. Here, we demonstrate high levels of cytotoxicity against solid tumour-derived cell lines with combination treatment utilizing Vgamma9Vdelta2 T cells, chemotherapeutic agents and the bisphosphonate, zoledronate. Pre-treatment with low concentrations of chemotherapeutic agents or zoledronate sensitized tumour cells to rapid killing by Vgamma9Vdelta2 T cells with levels of cytotoxicity approaching 90%. In addition, zoledronate enhanced the chemotherapy-induced sensitization of tumour cells to Vgamma9Vdelta2 T cell cytotoxicity resulting in almost 100% lysis of tumour targets in some cases. Vgamma9Vdelta2 T cell cytotoxicity was mediated by perforin following TCR-dependent and isoprenoid-mediated recognition of tumour cells. Production of IFN-gamma by Vgamma9Vdelta2 T cells was also induced after exposure to sensitized targets. We conclude that administration of Vgamma9Vdelta2 T cells at suitable intervals after chemotherapy and zoledronate may substantially increase antitumour activities in a range of malignancies.

Topics: Adenocarcinoma; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Burkitt Lymphoma; Carcinoma; Cell Line, Tumor; Cisplatin; Colorectal Neoplasms; Concanavalin A; Cytotoxicity, Immunologic; Diphosphonates; Doxorubicin; Drug Screening Assays, Antitumor; Drug Synergism; Etoposide; Female; Genes, T-Cell Receptor delta; Genes, T-Cell Receptor gamma; Humans; Imidazoles; Interferon-gamma; Lovastatin; Lung Neoplasms; Male; Membrane Glycoproteins; Neoplasms; Perforin; Pore Forming Cytotoxic Proteins; Prostatic Neoplasms; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocyte Subsets; Urinary Bladder Neoplasms; Vincristine; Zoledronic Acid

Current methods in the noninvasive detection and surveillance of bladder cancer via urine analysis include voided urine cytology (VUC) and some diagnostic urinary protein biomarkers; however, due to the poor sensitivity of VUC and high false-positive rates of currently available protein assays, detection of bladder cancer via urinalysis remains a challenge. In the study presented here, a rapid, high-sensitivity technique was developed to profile the N-linked glycoprotein component in naturally micturated human urine specimens. Concanavalin A (Con A) affinity chromatography coupled to nanoflow liquid chromatography was utilized to separate the complex peptide mixture prior to a linear ion trap MS analysis. Of 186 proteins identified with high confidence by multiple analyses, 40% were secreted proteins, 18% membrane proteins, and 14% extracellular proteins. In this study, the presence of several proteins appeared to be associated with the presence of bladder cancer, including alpha-1B-glycoprotein that was detected in all tumor-bearing patient samples but in none of the samples obtained from non-tumor-bearing individuals. The combination of Con A affinity chromatography and nano-LC/MS/MS provides an initial investigation of N-glycoproteins in complex biological samples and facilitates the identification of potential biomarkers of bladder cancer in noninvasively obtained human urine.

Topics: Amino Acid Sequence; Biomarkers, Tumor; Blood Proteins; Chromatography, Affinity; Chromatography, Liquid; Concanavalin A; Glycoproteins; Humans; Immunoglobulins; Mass Spectrometry; Molecular Sequence Data; Nanotechnology; Protein Array Analysis; Proteomics; Urinalysis; Urinary Bladder Neoplasms

The effect of fractions from a water extract of Polyporus on bladder tumor promotion was examined using 5% sodium saccharin (SS) in a short-term test with concanavalin A (Con A) in Wistar rats. Rats were given N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN) in drinking water for one week, and then promoter alone or test samples (given orally) plus promoter was administered for 3 weeks. Treatment with the BuOH fraction isolated from the water extract showed a strong inhibitory effect against the promoter. It was found that the inhibitory effect of the BuOH fraction is due to the effect of ergosterol contained in the fraction. Treatment with ergosterol showed a strong inhibitory effect against 5% SS, 0.01% BHBN, 3% DL-tryptophan (Trp) or 2% butylated hydroxyanisole (BHA); ID50 was 1.4 microg/kg/d, 2.9 microg/kg/d, 11.6 microg/kg/d, and 11.7 microg/kg/d against SS, BHBN, Trp and BHA, respectively. We also examined the effect of steroids and related compounds. Squalene and vitamin D2 showed strong inhibitory effect against 5% SS-induced bladder tumor promotion. These results strongly suggest that ergosterol could provide significant protection against the promotion of bladder tumor induced by many types of promoters in the environment.

Topics: Agglutination Tests; Algorithms; Animals; Antineoplastic Agents, Phytogenic; Basidiomycota; Butanols; Carcinogens; Chromatography, High Pressure Liquid; Concanavalin A; Diuretics; Dose-Response Relationship, Drug; Ergosterol; Male; Phytosterols; Plant Extracts; Rats; Rats, Wistar; Solvents; Urinary Bladder; Urinary Bladder Neoplasms; Water

ICR mice were treated with a carcinogen, N-butyl-N'-butanolnitrosoamine BBN), every day for 8 consecutive weeks and the effects of oral administration of edible mushrooms on the induction of urinary bladder carcinoma and on the activities of macrophages and lymphocytes were studied. Bladder carcinoma were found in all 10 mice (100%) treated with BBN alone, while we observed carcinoma only in 9 of 17 mice (52.9%), in 7 of 15 mice (46.7%) and 13 of 20 mice (65.0%) treated with Lentinus edodes, Grifola frondosa and Pleurotus ostreatus, respectively. Chemotactic activity of macrophages was suppressed in mice treated with BBN alone but maintained almost the normal level in mice treated with BBN plus Lentinus, Grifola or Pleurotus. Lymphocytes collected from mice treated with BBN plus each mushroom showed almost normal blastogenic response against concanavalin A, although those from mice treated with BBN alone completely retarded their response. Cytotoxic activity of lymphocytes against Yac-1 cells was also maintained at a normal level in mice treated with BBN plus each mushroom. Whereas in mice treated with BBN alone significant depression of NK cell activity occurred. Significantly higher cytotoxic activity against P-815 cells was observed in lymphocytes from mice treated with BBN plus each mushroom than that in lymphocytes from normal mice or mice treated with BBN alone.

Topics: Animals; Antibiotics, Antineoplastic; Basidiomycota; beta-Glucans; Butylhydroxybutylnitrosamine; Carcinogens; Cells, Cultured; Chemotaxis; Concanavalin A; Cytotoxicity, Immunologic; Disease Outbreaks; Eating; Female; Glucans; Lentinan; Lymphocyte Activation; Lymphocytes; Macrophages; Medicine, Traditional; Mice; Mice, Inbred ICR; Neoplasms; Polyporaceae; Polysaccharides; Spleen; Urinary Bladder Neoplasms

It is known that cytokine exert cytotoxic effect on certain tumor cell lines, as well as that cytokines production might be influenced by tumor cells. Therefore, serum and urine levels of TNF and IL-1 were determined by RIA in 20 patients with upper urinary tract cancer, 26 with urinary bladder cancer, and compared with those of 52 healthy blood bank donors. Serum levels of TNF in cancer patients were found moderately increased, and those of IL-1 unchanged. Conversely, urinary excretion of TNF was shown decreased in both upper urinary tract and urinary bladder cancer patients, while IL-1 excretion was not significantly changed. Tumor grade was not found to influence serum and urine levels of the cytokines studied. Unstimulated and PHA- and Con A-stimulated production of TNF by peripheral blood mononuclear cells was within the normal range, suggesting that other sources such as tumor cells have to be considered for the increase in the serum level. Basal production of IL-1 was lowered in patients with upper urothelial cancer. Further investigation are required to ascertain and reveal the possible mechanism of the decreased urinary excretion associated with increased serum levels of TNF in urinary tract cancer.

Topics: Concanavalin A; Female; Humans; Interleukin-1; Kidney Neoplasms; Male; Monocytes; Phytohemagglutinins; Reference Values; Tumor Necrosis Factor-alpha; Ureteral Neoplasms; Urinary Bladder Neoplasms

A derivative of ascorbic acid, 2-O-octadecylascorbic acid (CV-3611), is a strong scavenger of active oxygen species. We examined the effect of CV-3611 on a short-term test of bladder carcinogenesis, using concanavalin A (Con A)-dependent agglutination of isolated bladder epithelial cells. Rats were given 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) for 1 week, and then 5% sodium saccharin or 2% DL-tryptophan or 0.01% BHBN alone or with 0.002, 0.006 or 0.02% CV-3611 for 3 weeks. Treatment with CV-3611 reduced the effects of the bladder tumor promoters sodium saccharin and DL-tryptophan by 48-86 and 65-87%, respectively. CV-3611 also reduced the number of aggregates of bladder epithelial cells from rats treated with BHBN for 4 weeks. These results suggest that CV-3611 has a suppressive effect on rat bladder carcinogenesis.

Topics: Agglutination Tests; Animals; Ascorbic Acid; Butylhydroxybutylnitrosamine; Cell Aggregation; Concanavalin A; Free Radical Scavengers; Male; Rats; Saccharin; Tryptophan; Urinary Bladder Neoplasms

We studied the lectin binding patterns of 40 initial superficial and 10 subsequent invasive bladder tumors by the avidin-biotin-peroxidase complex (ABC) method using the following biotin-labeled lectins: PNA, DBA, UEA-I, BS-I, ConA and WGA. We observed the relationship between lectin binding and subsequent course of initial superficial tumors, grade and stage (T). DBA or WGA staining tumors and Con A negative tumors revealed no recurrence or superficial recurrence. Low grade tumors were DBA or BS-I positive and high grade tumors were ConA positive. Low staging tumors possessed DBA or WGA positiveness and high staging tumors had ConA positiveness. From these results we considered that negative staining of WGA or DBA, or positive staining of ConA was a change accompanying the malignant potentiality.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Transitional Cell; Concanavalin A; Female; Humans; Lectins; Male; Middle Aged; Peanut Agglutinin; Plant Lectins; Urinary Bladder Neoplasms; Wheat Germ Agglutinins

The effect of three lectins, Ricinus communis agglutinin (RCA II), concanavalin agglutinin (ConA), and wheat germ agglutinin (WGA), on KK-47 bladder cancer cell line was studied, RCA II showed effective inhibition of H3-uridine and H3-thymidine uptake by KK-47. ConA showed a stimulatory effect in all three concentrations used. WGA also showed stimulatory effect, but it was less pronounced than ConA.

Topics: Carcinoma; Concanavalin A; Humans; Kinetics; Lectins; Plant Lectins; Plants, Toxic; Ricinus communis; Thymidine; Tumor Cells, Cultured; Uridine; Urinary Bladder Neoplasms; Wheat Germ Agglutinins

The thymus humoral factor (THF) was extracted from the bovine calf thymus, and its effect on the non-specific cellular immune response of 34 bladder carcinoma patients was studied using the modified micro-whole blood culture method. As a result, in the early stage of bladder carcinoma, the immuno-deficient state of the lymphocytes was restored under the influence of THF, in vitro, but in the terminal stage of bladder carcinoma, the effect of THF was not observed. This difference was clear between the low stage group and high stage group. This fact indicates that the accumulation of precursor T cells occurs in the peripheral blood of the patients of low stage bladder carcinoma, and THF is thought to be effective on T cell maturation. In the late stage of bladder carcinoma, disturbance of the production of immature T cells in the bone marrow is suspected.

Topics: Aged; Animals; Cattle; Cells, Cultured; Concanavalin A; Female; Humans; Immunity, Cellular; Lymphocyte Activation; Male; Middle Aged; T-Lymphocytes; Thymus Hormones; Urinary Bladder Neoplasms

Binding sites for lectins of peanuts, soya-beans and concanavalin A were identified in the tissues of normal human urinary bladder and its transitional cell tumors (31 patients) using the lectin-peroxidase technique. No binding sites for any of the lectins were found in normal urothelium. Receptors for peanut and soya-bean lectins were observed on the plasma membranes of 20% of tumor cells in transitional cell papillomas. A diffuse distribution of those lectins in tumor cell cytoplasm was interpreted as a tendency to malignant transformation of tumor. There were no concanavalin A receptors in tumor cells.

Topics: Acetylgalactosamine; Adult; Aged; Aged, 80 and over; Carcinoma, Transitional Cell; Concanavalin A; Galactose; Histocytochemistry; Humans; Lectins; Male; Mannose; Middle Aged; Papilloma; Peanut Agglutinin; Plant Lectins; Receptors, Mitogen; Soybean Proteins; Urinary Bladder; Urinary Bladder Neoplasms

In an attempt to delineate the role of tumor-cell motility in the process of invasion, we compared the migration of NBT II in a two-dimensional migration assay with its migration in a three-dimensional invasion assay. Both systems were maintained with and without succinylated concanavalin A (s-Con A) dissolved in the culture medium. This lectin has a reversible inhibitory effect on the migration of cells in vitro. The migration of NBT-II aggregates, seeded in flasks containing 200 micrograms/ml s-Con A or without s-Con A, was studied by time-lapse photomicrography. In the presence of s-Con A, migration was immediately stopped. When the treated medium was replaced by culture medium to which 10 mM alpha-methyl-mannose was added, the inhibition of migration was abolished. The invasive capacity of NBT II in the presence or absence of s-Con A was studied by confronting precultured fragments of 9- to 11-day-old embryonic chick heart (0.4 mm in diameter) with NBT-II aggregates (0.2 mm) made in the presence or absence of s-Con A. Light microscopy showed no difference in the extent of invasion. To demonstrate the presence of s-Con A in the invading tumor cells, immunoperoxidase staining for Con A was done. The treated cultures stained positively while the controls were negative. The data presented here question the correlation between tumor-cell motility in two-dimensional system and the invasive behavior of these cells in three dimensions, and implies that the ability or inability of cells to migrate on plastic does not necessarily reflect their invasiveness in vitro.

Topics: Animals; Carcinoma; Cell Line; Cell Movement; Concanavalin A; Epithelium; Methods; Neoplasm Invasiveness; Rats; Rats, Inbred Strains; Urinary Bladder Neoplasms

The promoting effects of various chemicals and dietary constituents on bladder carcinogenesis were examined by means of a short-term assay, in which maintenance of concanavalin A agglutination of isolated rat bladder cells caused by a subcarcinogenic dose of N-butyl-N-(4-hydroxybutyl)nitrosamine was used as an indicator. Twenty-seven chemicals were examined as possible promoters. Positive results in this assay were consistent with established promoting effects in the cases of sodium saccharin, saccharin, sodium L-ascorbate, sodium cyclamate, DL-tryptophan, butylated hydroxyanisole, butylated hydroxytoluene, L-thioproline and phenacetin. Allopurinol was the only established promoter that gave negative results in the agglutination assay. Thus, this method is useful for rapid evaluation of the specific promoting effect of a chemical on bladder carcinogenesis.

Topics: Agglutination Tests; Animals; Butylhydroxybutylnitrosamine; Carcinogens; Cocarcinogenesis; Concanavalin A; Drug Evaluation, Preclinical; In Vitro Techniques; Male; Rats; Rats, Inbred F344; Urinary Bladder Neoplasms

Topics: Administration, Topical; Animals; Antineoplastic Agents; Bleomycin; Carcinoma, Transitional Cell; Concanavalin A; HeLa Cells; Mice; Urinary Bladder Neoplasms

Agglutination of rat urinary bladder epithelial cells by concanavalin A (Con A) has been reported to be an early marker of bladder carcinogenesis. Ulceration of the bladder, induced by cyclophosphamide (CP) or freezing, followed by sodium saccharin in the diet results in the induction of bladder cancer. In the present studies, the agglutination of rat urinary bladder epithelial cells by Con A was shown to be increased during the regenerative hyperplasia following ulceration induced by i.p. CP injection, but it returned to normal levels by Day 21 when the preparative process was nearly complete. This effect correlated quantitatively with the dose of CP. However, if CP administration was followed by sodium saccharin in the diet beginning 14 days after the injection, the agglutinability of bladder cells by Con A persisted. In contrast, agglutination of bladder cells by Con A during regenerative hyperplasia following ulceration induced by freezing was not increased whether sodium saccharin was fed or not. These results indicate that Con A agglutination distinguishes between the regenerative hyperplasia induced by CP or freezing, even though either method followed by sodium saccharin in the diet results in bladder cancer in the rat.

Topics: Agglutination; Animals; Carcinogens; Concanavalin A; Cyclophosphamide; Dose-Response Relationship, Drug; Epithelium; Freezing; Hyperplasia; Male; Rats; Rats, Inbred F344; Saccharin; Ulcer; Urinary Bladder; Urinary Bladder Diseases; Urinary Bladder Neoplasms

A tumor-associated antigen was preliminarily identified in urine from bilharzial (squamous-cell carcinoma) bladder cancer patients. Monospecific rabbit antisera were made by immunization with concentrated bladder cancer urine and exhaustive absorption with insoluble normal human serum and urine. The urine tumor-associated antigen was identical to an antigen from 3M KCl bladder tumor extract by immunodiffusion. The antigen in urine was found in nine of 10 bladder cancer patients and was absent from normal urine and serum by immunodiffusion and immunoelectrophoresis. The antigen was a concanavalin-A-binding glycoprotein which was anodal on immunoelectrophoresis. It was stable up to 2 years at -20 degrees C and did not cross-react with carcinoembryonic antigen or with Schistosoma haematobium antigens.

Topics: Adult; Antigens, Neoplasm; Carcinoma, Squamous Cell; Chromatography, Affinity; Concanavalin A; Glycoproteins; Humans; Immunodiffusion; Immunoelectrophoresis, Two-Dimensional; Male; Urinary Bladder Neoplasms

Topics: Animals; Butylhydroxybutylnitrosamine; Cattle; Concanavalin A; In Vitro Techniques; Lymphocyte Activation; Rats; Rats, Inbred Strains; Thymus Hormones; Urinary Bladder Neoplasms

Biphenyl and its derivatives, 2-aminobiphenyl, 2-nitrobiphenyl, 4-aminobiphenyl, 4-nitrobiphenyl, p-phenylphenol, o-phenylphenol (OPP), and o-phenylphenol sodium salt tetrahydrate (OPP-Na) were examined for their bladder carcinogenicity in rats by a short-term assay for agglutinability of bladder epithelial cells with concanavalin A. Increased agglutinability was observed after 1-week treatment with 2.0% and 1.0% OPP, 2.0% and 1.0% OPP-Na, 0.5 and 0.1% 4-aminobiphenyl, and 0.5% 4-nitrobiphenyl in the diet, suggesting carcinogenicity of these compounds in the bladder. Such an increase in agglutinability was not observed in rats fed diets containing biphenyl, 2-aminobiphenyl, 2-nitrobiphenyl or p-phenylphenol at 2.0%. With OPP-Na, an in vivo carcinogenesis experiment was performed. Bladder carcinomas developed in 14 of 36 male Fisher rats fed a 2% OPP-Na diet for 50 weeks.

Topics: Agglutination Tests; Animals; Biphenyl Compounds; Concanavalin A; Epithelial Cells; Male; Rats; Rats, Inbred F344; Urinary Bladder Neoplasms

The susceptibility of analbuminemic rats, a mutant strain of Sprague-Dawley rats, to bladder carcinogens was examined by testing the agglutinability of isolated bladder epithelial cells by Concanavalin A (Con A). One-week treatment with 0.001% N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) in the drinking water or 0.01% N-(4-(5-nitro-2-furyl)-2-thiazolyl)-formamide (FANFT), 0.01% and 0.1% 4-aminobiphenyl, 0.1% 4-nitrobiphenyl, 0.1% benzidine, 0.1% 2-napthylamine or 5% sodium saccharin in the diet clearly induced high agglutinability of bladder cells of male analbuminemic rats but not Sprague-Dawley rats. These results suggest that male analbuminemic rats are very susceptible to bladder carcinogens in general and therefore will be very useful in screening tests for bladder carcinogens.

Topics: 2-Naphthylamine; Agglutination Tests; Aminobiphenyl Compounds; Animals; Butylhydroxybutylnitrosamine; Carcinogens; Cells, Cultured; Concanavalin A; Diet; Disease Susceptibility; Drug Evaluation, Preclinical; FANFT; Male; Rats; Rats, Inbred Strains; Saccharin; Serum Albumin; Urinary Bladder; Urinary Bladder Neoplasms

The effects of amino acids on the enhanced agglutinability of bladder cells with concanavalin A induced by subcarcinogenic treatment with N-butyl-N-(4-hydroxybutyl)nitrosamine were examined. The amino acids examined were L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-cysteine, L-glutamic acid, L-glutamine, L-glycine, DL- and L-histidine, L-hydroxyproline, L-isoleucine, D- and L-leucine, L-lysine, L-methionine, DL- and L-phenylalanine, L-proline, L-serine, L-threonine, DL-, D- and L-tryptophan, L-tyrosine and D- and L-valine. They were added to powdered diet at a concentration of 2.0%. L-Leucine, L-isoleucine, L-valine, DL- and D-tryptophan prolonged the period during which the bladder cells showed enhanced agglutinability with concanavalin A. Leupeptin, a protease inhibitor, and L-leucyl-L-leucine were also examined at a concentration of 0.1% because of their similar chemical structures, and were found to have the same effect. The tumor-promoting effects of DL-tryptophan and leupeptin have already been established by in vivo carcinogenesis experiments. The effects of L-leucine, L-isoleucine, L-valine, D-tryptophan and L-leucyl-L-leucine, detected by this short term assay, suggest that these compounds may also be promoters of bladder cancer in rats.

Topics: Amino Acids; Animals; Butylhydroxybutylnitrosamine; Cell Aggregation; Cocarcinogenesis; Concanavalin A; Male; Rats; Rats, Inbred Strains; Urinary Bladder; Urinary Bladder Neoplasms

Saccharin is known to have a tumor-promoting effect on bladder cancer in rats, but its mechanism of action is unknown. We demonstrated that the increased agglutinability of isolated epithelial cells of the bladder in the presence of concanavalin A caused by a subcarcinogenic dose of bladder carcinogens disappeared shortly after the end of their administration. However, saccharin maintained the increased agglutinability when given continuously after administration of carcinogen. Moreover, the agglutinability of bladder cells previously exposed to a subcarcinogenic dose of bladder carcinogens increased again when saccharin was given after the agglutinability had disappeared completely.

Topics: Animals; Butylhydroxybutylnitrosamine; Cell Aggregation; Cell Membrane; Cocarcinogenesis; Concanavalin A; Diet; FANFT; Male; Neoplasms, Experimental; Precancerous Conditions; Rats; Rats, Inbred Strains; Saccharin; Urinary Bladder; Urinary Bladder Neoplasms

Concanavalin A (Con A)-inducible suppressor cell activity in peripheral blood lymphocytes (PBL) of urologic cancer patients and of appropriate controls with benign urologic disorders was measured concurrently. Although the proliferative responses to Con A of the cancer patients were significantly lower than those of controls, no difference in Con A-induced suppressor cell activity was demonstrated between cancer patients and controls when tested under a variety of conditions. Moreover, regression analysis revealed no correlation between the proliferative response to Con A and suppressor cell activity in either cancer patients or controls. The results indicated that Con A-inducible suppressor cell activity was unaltered in urologic cancer patients and suggested that suppressor cells of the type that can be activated by Con A were not involved in the general immunologic impairment frequently associated with urologic cancer.

Topics: Adenocarcinoma; Concanavalin A; Female; Humans; Kidney Calculi; Kidney Neoplasms; Lymphocyte Activation; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatitis; T-Lymphocytes, Regulatory; Urethral Stricture; Urinary Bladder Neoplasms; Urinary Tract Infections; Urogenital Neoplasms

The agglutination by concanavalin A of isolated epithelial cells of the rat bladder was examined after in vivo treatment of rats with various bladder carcinogens for one week. The carcinogens tested were N-butyl-N-(4-hydroxybutyl)nitrosamine, dibutylnitrosamine, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, 2-acetylaminofluorene, 2-napthylamine, benzidine, N-methyl-N-nitrosourea, and cyclophosphamide, and they were given to male Wistar rats p.o., s.c., intravesically, or i.p. As negative controls, the effects of administration of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, dimethylnitrosamine, N-methyl-N'-nitro-N-nitrosoguanidine, and surgical implantation of glass beads in the bladder were also tested. One week after the start of treatment, epithelial cells were isolated from the bladder by sonication, and agglutination of the isolated cells with concanavalin A was assayed. The observed agglutinabilities of isolated cells were found to be closely correlated with the reported bladder carcinogenicities of these chemicals in rats. Thus, concanavalin A agglutination of bladder cells should be a useful rapid in vivo mammalian system for screening bladder carcinogens.

Topics: 2-Acetylaminofluorene; 2-Naphthylamine; Benzidines; Carcinogens; Cell Aggregation; Concanavalin A; Cyclophosphamide; Drug Evaluation, Preclinical; Methylnitrosourea; Nitrosamines; Urinary Bladder; Urinary Bladder Neoplasms

Longitudinal experiments were performed in which lymphocytes from patients were compared with simultaneously studied normals. Patient lymphocytes were examined for their ability to function as stimulator and responder cells in a one-way MLC. Additionally, lymphocyte mitogenic response to PHA and Con A were examined. We observed changes in these parameters that could be correlated with the clinical course of the patients.

Topics: Carcinoma, Transitional Cell; Concanavalin A; Humans; In Vitro Techniques; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Male; Middle Aged; Phytohemagglutinins; Time Factors; Urinary Bladder Neoplasms

Patients with transitional cell carcinoma of the bladder have a highly significant stepwise decrease in responsiveness to challenge with DNCB with advancing stage of disease. Seventy-five percent of those patients with superficial tumors are skin-test positive versus only 35% for those having tumors that are locally advanced and/or metastatic. MLC response and ability to stimulate in this culture as well as PHA and Con A response of blood leukocytes have been studied in relation to stage of disease and therapy. Recent irradiation appears to inhibit significantly MLC responsiveness, and PHA and Con A blastogenesis. Although responsiveness for this group of patients is decreased from normal, a further decrease occurs in responsiveness to Con A with advancing stage of disease. Blood leukocytes from some patients with urinary bladder carcinoma appear to have a decreased ability to function as stimulator cells in one-way MLC. This ability to stimulate returns to normal levels with tumor removal.

Topics: Carcinoma, Transitional Cell; Concanavalin A; Dinitrochlorobenzene; Humans; In Vitro Techniques; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Male; Phytohemagglutinins; Skin Tests; Urinary Bladder Neoplasms

Concanavalin A (Con A) and phytohemagglutinin (PHA) responses of spleen and blood lymphocytes from tumor-bearing (TB) rats were found to be markedly depressed in 4 different models employing tumors of spontaneous origin. Removal of phagocytic cells from both spleen and blood lymphocyte suspensions led to a complete restoration of the responses, indicating that the decreased responses were not due to intrinsic defects in the lymphocytes. The reduction was shown to be due to the inhibitory effect of an increase in the percentage of phagocytic cells. In addition, TB induced an atrophy of the thymus and a decrease in the number of thymic lymphocytes, mainly due to severe lymphocyte depletion in the cortex. The cells that remained in the thymus exhibited increased responsiveness to PHA and Con A as compared to thymus cells from normal rats. Similar results were found in hydrocortisone acetate-treated rats, suggesting that TB leads to a decrease in nonresponsive, cortical corticosteroid-sensitive thymocytes.

Topics: Animals; Carcinoma; Concanavalin A; Female; Lectins; Lymphocyte Activation; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Spleen; T-Lymphocytes; Thymus Gland; Transplantation Immunology; Urinary Bladder Neoplasms

N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), which is a potent, specific bladder carcinogen in rats, and its related compounds were orally administered to rats for 1 week. The bladder cells were isolated by the treatment with EDTA and sonication and they were subjected to agglutination assay by concanavalin A (Con A). Bladder cells obtained from rats treated with BBN, N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) and N-butyl-N-(2-hydroxyethyl)nitrosamine (BHEN) were agglutination-positive, while those cells treated with N-tert-butyl-N-(4-hydroxybutyl)-nitrosamine (t-BBH) and N-butyl-N-(3-hydroxypropyl)nitrosamine (BHPN) were negative. Results obtained by this method were highly correlated with the known carcinogenicity of BBN and its analogues. Therefore, this method could be used for rapid screening of bladder carcinogens.

Topics: Animals; Butylhydroxybutylnitrosamine; Carcinogens; Cell Aggregation; Concanavalin A; Drug Evaluation, Preclinical; Humans; In Vitro Techniques; Male; Neoplasms, Experimental; Precancerous Conditions; Rats; Urinary Bladder; Urinary Bladder Neoplasms