concanavalin-a and Kidney-Neoplasms

Interleukin-2 plays a crucial role in enhancing the antitumor immune response. Clinical trials, mainly in renal cell carcinoma and melanoma patients, have been carried out with encouraging results. Recent reports demonstrated that interleukin-2 therapy may depress the immune response either in vitro or in vivo. We decided to monitor, in nine renal cancer patients, the proliferative responses and the parallel variations in Ca2+ homeostasis of peripheral blood lymphocytes collected before, during and after the first cycle of a 3-day interleukin-2 systemic administration. The proliferative response to phytohemagglutinin or concanavalin A significantly dropped early during interleukin-2 infusion. Consistently, an impairment in mobilizing Ca2+, either from internal stores or via influx from outside, was observed. Results obtained with a mAb-alpha CD3 molecular complex strongly suggested that the TCR/CD3 signal transduction pathway was defective. In contrast, no major variations were observed in the general machinery controlling Ca2+ homeostasis nor in the total Ca(2+)-releasable pool. Patients' lymphocytes, cultured in vitro for 3 days in medium alone, showed an almost complete recovery in their ability to respond to mitogens. In conclusion, we show that interleukin-2 administration in cancer patients induces a reversible state of anergy in circulating lymphocytes, assessed both by the reduction in the proliferative response and the block of the mitogen-activated intracellular Ca2+ signalling.

Topics: Calcium; Carcinoma, Renal Cell; Cells, Cultured; Concanavalin A; Homeostasis; Humans; Immunotherapy; Interleukin-2; Ionomycin; Kidney Neoplasms; Lymphocyte Activation; Lymphocytes; Muromonab-CD3; Phytohemagglutinins; Recombinant Proteins; Second Messenger Systems; Signal Transduction; Stimulation, Chemical; Terpenes; Thapsigargin

We investigated the immunomodulatory capacity of primary cultures of renal cell carcinomas (RCC) by assessing production of cytokines and modulation of mitogen-induced T lymphocyte blast transformation. The results clearly show that immunomodulatory capacity is a common feature of RCC and that in vitro these tumors can produce interleukin-10 (IL-10) up to 20 ng/ml, IL-6 up to 35 micrograms/ml (> 250 kU/ml in the B9 system), IL-11 up to 15 micrograms/ml, and transforming growth factor-beta 1 (TGF-beta 1) up to 22 ng/ml. Furthermore, these tumors have the capacity to modulate T cell blast transformation over two orders of magnitude in each direction. The correlations of the immunologic properties of tumor cell cultures with the conventional classification of tumors (histology, cytology, staging, grading, presence of metastases, and secondary tumors) are analyzed. The significance of these findings for modulation of local immunity by RCC as well as for patient outcome is discussed.

Topics: Adjuvants, Immunologic; Carcinoma, Renal Cell; Concanavalin A; Humans; Interleukin-10; Interleukin-11; Interleukin-6; Interleukins; Kidney Neoplasms; Lymphocyte Activation; Mitogens; Reference Values; T-Lymphocytes; Transforming Growth Factor beta; Tumor Cells, Cultured

Long-Evans (Eker) rats carry a mutation that predisposes them to develop spontaneous renal cell tumors of two morphologic patterns: solid chromophilic masses or cystic lesions lined by eosinophilic cells. Previous studies have suggested that these tumors arise from the proximal tubules. In the present study, lectin-binding characteristics and cytokeratin expression of various stages of hereditary rat renal epithelial neoplasia were examined to localize the portion of the nephron from which tumors arise. Lectin-binding histochemistry has been used as a marker of cell surface glycoprotein expression, thought to be important in the differentiation of benign from malignant epithelial lesions and in the determination of their cell of origin. The presence or absence of keratin intermediate filaments in the rat nephron has been used to identify nephron segments. The polyclonal antibody to high- and low-molecular-weight cytokeratin stained the cells of the collecting ducts but not the proximal or distal tubules. Binding to the proximal tubules by the lectins Conavalia ensiformis (Con A), Dolichas biflorus, Ricinus communis (RCA-1), and Triticum vulgare and to the distal tubules by Con A, RCA-1, Arachis hypogaea (PNA) with and without neuraminidase, and the antibody for cytokeratins was demonstrated. The lectin binding and cytokeratin staining patterns of rat hereditary renal cell carcinoma, adenoma and the preneoplastic lesions of atypical tubules and hyperplasias suggest that cystic adenomas arise from the distal nephron, principally the collecting duct, whereas the solid atypical tubules, hyperplasias, and adenomas arise from the proximal nephron, principally the proximal tubule.

Topics: Adenoma; Animals; Biomarkers, Tumor; Carcinoma, Renal Cell; Concanavalin A; Histocytochemistry; Hyperplasia; Immunohistochemistry; Keratins; Kidney Neoplasms; Kidney Tubules, Distal; Kidney Tubules, Proximal; Lectins; Male; Plant Lectins; Precancerous Conditions; Rats; Rodent Diseases; Wheat Germ Agglutinins

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

The enzymatic and immunological nature, and the sugar chain structure, of gamma-glutamyl transferase (GGT) purified from tissues of benign prostatic hypertrophy (BPH), prostatic carcinoma (PCa) and renal cell carcinoma (RCa), were compared with those of the normal prostate (NP) and kidney (NK). The specific activities of GGTs in NP, NK, BPH, PCa and RCa were 78.9, 22.5, 105, 92.5 and 52.5 mU/mg protein, respectively. The molecular masses of GGTs from BPH, PCa and RCa were 72 kDa, 78 and 108 kDa, and 79 and 105 kDa, respectively. The Michaelis constants (Km), optimum pHs and the inhibition of GGT activities by several chemical compounds, revealed that the GGT from BPH, PCa and RCa was similar to that of normal GGT. Immunologically, the IgG fraction against anti-human seminal plasma GGT fused to the all of the GGTs tested. The sugar chain heterogeneities of the various GGTs, detected by the serial-lectin affinity technique, differed from one another. The sugar chain of GGT from BPH resembled the sugar chain from NP. On the contrary, the sugar chains of GGTs from PCa and RCa were markedly different from those from normal tissues. In the GGT from PCa, multi-antennary complex type sugar chains were more increased than the enzyme of NP. In general, as previously reported, the sugar chains of GGTs from carcinomatous tissues of prostate and kidney had an increased content of bisecting GlcNAc (beta 1-->4) containing complex type sugar chains. Moreover, the reductions of the biantennary complex type sugar chain with fucose linkage and the hybrid type sugar chain were obvious in the GGT from carcinomatous tissues of the prostate and kidney.

Topics: Adult; Aged; Chromatography, Affinity; Concanavalin A; gamma-Glutamyltransferase; Humans; Hydrogen-Ion Concentration; Immunodiffusion; Kidney; Kidney Neoplasms; Kinetics; Lectins; Male; Middle Aged; Molecular Weight; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Concanavalin A (Con A)-induced suppressor cell activity against the proliferative response of autologous lymphocytes to phytohemagglutinin was examined in peripheral blood lymphocytes derived from 12 normal control subjects and 25 patients with renal cell carcinoma (RCC). The Con A-induced suppressor cell activity in patients with RCC (23.4 +/- 21.4%) was significantly higher than that in control subjects (9.7 +/- 10.7%, P less than 0.05). No significant difference between the degree of suppressor cell activity and stage of disease, grade of malignancy, or cell type was found, although the suppressor activity in patients with tumor microscopically infiltrated by lymphocytes was significantly higher than in patients without lymphocyte-infiltration into the tumor (P less than 0.05). Furthermore, compared with control subjects, Con A-induced suppressor activity in patients with high stage and in those with lymphocyte infiltration into the tumor was significantly higher (P less than 0.05 and P less than 0.01, respectively). In conclusion, because patients with RCC have high suppressor cell activity, abrogation of this activity may be necessary to treat the RCC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; Concanavalin A; Female; Humans; Kidney Neoplasms; Male; Middle Aged; T-Lymphocytes, Regulatory

The effect of lectins on cultured renal cell carcinoma and normal renal cells was studied. Ricin II showed effective inhibition of 3H-uridine and 3H-thymidine uptake by renal cell carcinoma and normal renal cells in all cases. Normal renal cells were more resistant to the inhibitory effect of ricin II as compared to renal cell carcinoma. Concanavalin agglutinin and wheat germ agglutinin led to stimulation of 3H-uridine and 3H-thymidine uptake by renal cell carcinoma and normal renal cells at low concentrations (0.2 micrograms/ml), and to suppression at high concentrations (2 and 20 micrograms/ml).

Topics: Carcinoma, Renal Cell; Cells, Cultured; Concanavalin A; Humans; In Vitro Techniques; Kidney; Kidney Neoplasms; Kinetics; Lectins; Plant Lectins; Thymidine; Uridine; Wheat Germ Agglutinins

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

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Concanavalin A; Female; Humans; Immunity, Cellular; Kidney Neoplasms; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Tuberculin Test

Topics: Adenocarcinoma; Agglutination; Animals; Antigens, Neoplasm; Anura; Ascites; Cell Line; Cell Membrane; Cell Nucleus; Concanavalin A; Inclusion Bodies; Kidney Neoplasms; Rana pipiens

The in vivo tumorigenicity of malignant mouse-nonmalignant human somatic cell hybrids was correlated with the in vitro characteristics. The renal adenocarcinoma mouse cell line RAG and the normal, diploid human cell line Wl-38 were used as the fusion parents. Five independent RAG Wl 38 hybrid clones were tested for concanavalin A (Con A) agglutination patterns, in vitro invasiveness, and tumor formation in immunosuppressed mice. Tests on the parental lines showed that RAG cells agglutinated at much lower levels of Con A than the Wl-38 cells. RAG cells overgrew Wl-38 cells in the in vitro invasiveness assay. RAG cells readily formed tumors in untreated adult or young immunosuppressed mice, whereas the Wl-38 cells did not. The five hybrid clones were all similar, since they had Con A agglutination levels intermediate to those of both parents, though patterns were more "tumor-like", overgrew the Wl-38 cells in the invasiveness assay, and formed tumors in immunosuppressed mice.

Topics: Adenocarcinoma; Agglutination; Animals; Cell Division; Chromosomes; Concanavalin A; Humans; Hybrid Cells; Immunosuppression Therapy; Kidney Neoplasms; Male; Mice; Neoplasms, Experimental

Topics: Agglutination Tests; Animals; Cell Survival; Cell Transformation, Neoplastic; Concanavalin A; Culture Techniques; Kidney; Kidney Neoplasms; Mitosis; Nitrosamines; Platelet Adhesiveness; Rats

Topics: Allantois; Animals; Carboxymethylcellulose Sodium; Cell Aggregation; Cell Division; Cell Nucleolus; Cells, Cultured; Clone Cells; Concanavalin A; Kidney Neoplasms; Neoplasms, Experimental; Rats