concanavalin-a and Carcinoma--Squamous-Cell

The prevalence of oral squamous cell carcinoma (OSCC) is high in South and Southeast Asia regions. Most OSCC patients are detected at advanced stages low 5-year survival rates. Aberrant expression of glycosylated proteins was found to be associated with malignant transformation and cancer progression. Hence, identification of cancer-associated glycoproteins could be used as potential biomarkers that are beneficial for diagnosis or clinical management of patients. This study aims to identify the differentially expressed glycoproteins using lectin-based glycoproteomics approaches. Serum samples of 40 patients with OSCC, 10 patients with oral potentially malignant disorder (OPMD), and 10 healthy individuals as control group were subjected to two-dimensional gel electrophoresis (2-DE) coupled with lectin Concanavalin A and Jacalin that specifically bind to N- and O-glycosylated proteins, respectively. Five differentially expressed N- and O-glycoproteins with various potential glycosylation sites were identified, namely N-glycosylated α1-antitrypsin (AAT), α2-HS-glycoprotein (AHSG), apolipoprotein A-I (APOA1), and haptoglobin (HP); as well as O-glycosylated AHSG and clusterin (CLU). Among them, AAT and APOA1 were further validated using enzyme-linked immunosorbent assay (ELISA) (n = 120). It was found that AAT and APOA1 are significantly upregulated in OSCC and these glycoproteins are independent risk factors of OSCC. The clinical utility of AAT and APOA1 as potential biomarkers of OSCC is needed for further evaluation.

Topics: Adult; Aged; alpha 1-Antitrypsin; Apolipoprotein A-I; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Chromatography, Affinity; Chromatography, Agarose; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins; Glycosylation; Humans; Male; Mass Spectrometry; Middle Aged; Mouth Neoplasms; Plant Lectins; Precancerous Conditions; Squamous Cell Carcinoma of Head and Neck

The capacity of cell immunity to act against tumor cells has been presented as a decisive influence in the prognosis of patients with cancer. The aim of this study was to evaluate lymphoproliferation in nonadherent peripheral blood cell cultures of patients with advanced supraglottic laryngeal cancer.. Fourteen patients with advanced supraglottic laryngeal cancer were studied prospectively. Lymphoproliferation was quantified by adding 3H-thymidine and measured in counts/minute using liquid scintillation spectrometry. Based on the ratio between stimulated and baseline cultures, the proliferation index was calculated before and 236 +/- 18 days after the surgery.. Lymphoproliferation was lower in patients than in healthy controls (P = .01) in the preoperative as well as in the late postoperative period (P = .006 and P = .02, respectively). However, there was no change from preoperative to late postoperative.. Pre- and postoperative results show that patients with advanced supraglottic laryngeal cancer present lymphoproliferation diminished before the surgery, and in the late postoperative period, there was no recovery of immune capacity evaluated by lymphoproliferation measurement.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Case-Control Studies; Concanavalin A; Female; Follow-Up Studies; Humans; Laryngeal Neoplasms; Leukocytes, Mononuclear; Lymphocyte Activation; Male; Middle Aged; Mitogens; Neoplasm Staging; Prospective Studies; Radiopharmaceuticals; Recovery of Function; Thymidine; Tritium

We have shown that the sera of lung cancer patients affect the response of ConA-stimulated normal peripheral blood mononuclear cells by decreasing the expression of IL-2Ralpha and inhibiting the release of IL-1beta and IL-2. A tendency to enhance the release of IL-6 was also observed. We conclude that an imbalance in the Th1/Th2 cytokine response, typical for cancer patients, may at least partly be related to soluble factors circulating in the patients' blood. We discuss a putative role of serum IL-10, IL-1ra, and soluble IL-2Ralpha in the effects observed.

Topics: Adenocarcinoma; Adult; Aged; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Concanavalin A; Cytokines; Female; Humans; Interleukin-2 Receptor alpha Subunit; Lung Neoplasms; Male; Middle Aged; Monocytes; Receptors, Interleukin; Receptors, Interleukin-2; Serum

We evaluated the efficiency of recombinant vaccinia virus expressing interleukin-2 (rvv-IL-2) as a tumor vaccine in an immunocompetent mouse model of head and neck squamous cell carcinoma (SCC VII/SF). Mice with five-day-old tumors in the floor of the mouth were treated with rvv-IL-2 by intratumoral injections. These treated mice survived longer (P <.03) than mice treated with control vaccines. Splenocytes, bone marrow, and lymph node cells from tumor-bearing mice responded poorly to concanavalin A stimulation, suggesting induction of immunosuppression. The rvv-IL-2 virus grew for 7 days in the tumor following intratumoral injection. We did not detect any virus particles in several normal organs following rvv-IL-2 injection. Comparison of expression levels of several potential immune inhibitory mediators between the tumors growing in mice and cultured tumor cells demonstrated higher expression of IL-10, GM-CSF, TGF-beta, and NO synthetase in tumors. These results suggested possible roles for these molecules in immunosuppression. We conclude that rvv-IL-2 has potential as a therapeutic vaccine for head and neck cancer and that it can be more effective provided the immunosuppression is reversed.

Topics: Animals; Bone Marrow; Carcinoma, Squamous Cell; Concanavalin A; DNA Primers; Genetic Therapy; Genetic Vectors; Granulocyte-Macrophage Colony-Stimulating Factor; Head and Neck Neoplasms; Humans; Immunosuppression Therapy; Interleukin-10; Interleukin-2; Lymph Nodes; Mice; Neoplasm Transplantation; Nitric Oxide Synthase; Reverse Transcriptase Polymerase Chain Reaction; Spleen; Survival Rate; T-Lymphocytes; Transforming Growth Factor beta; Vaccinia virus

To prepare polymeric vesicles and niosomes bearing glucose or transferrin ligands for drug targeting.. A glucose-palmitoyl glycol chitosan (PGC) conjugate was synthesised and glucose-PGC polymeric vesicles prepared by sonication of glucose-PGC/cholesterol. N-palmitoylglucosamine (NPG) was synthesised and NPG niosomes also prepared by sonication of NPG/ sorbitan monostearate/ cholesterol/ cholesteryl poly-24-oxyethylene ether. These 2 glucose vesicles were incubated with colloidal concanavalin A gold (Con-A gold), washed and visualised by transmission electron microscopy (TEM). Transferrin was also conjugated to the surface of PGC vesicles and the uptake of these vesicles investigated in the A431 cell line (over expressing the transferrin receptor) by fluorescent activated cell sorter analysis.. TEM imaging confirmed the presence of glucose units on the surface of PGC polymeric vesicles and NPG niosomes. Transferrin was coupled to PGC vesicles at a level of 0.60+/-0.18 g of transferrin per g polymer. The proportion of FITC-dextran positive A431 cells was 42% (FITC-dextran solution), 74% (plain vesicles) and 90% (transferrin vesicles).. Glucose and transferrin bearing chitosan based vesicles and glucose niosomes have been prepared. Glucose bearing vesicles bind Con-A to their surface. Chitosan based vesicles are taken up by A431 cells and transferrin enhances this uptake.

Topics: Carcinoma, Squamous Cell; Chitin; Chitosan; Concanavalin A; Dextrans; Drug Carriers; Drug Delivery Systems; Fluorescein-5-isothiocyanate; Glucose; Glycolipids; Gold; Humans; Ligands; Surface-Active Agents; Transferrin; Tumor Cells, Cultured

Seventy newly diagnosed Caucasian male patients with head and neck squamous cell carcinomas (HNSCC) were included in the study. All patients were less than 80 years of age, with no cachexia or auto-immune disease, and they were not taking immuno-active medications. Monocytes from these patients were cultured in vitro and supplemented with autologous serum under ex vivo conditions or cultured with serum-free medium. Comparison was made to monocytes from 59 patients with benign HN diseases. Similar physical activity levels prior to testing as well as a minimum stress load were ensured in both groups. Increased monocyte supernatant levels were determined under ex vivo conditions of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha, but not of interleukin-12 (IL-12) with endotoxin stimulated monocytes of HNSCC patients compared to control conditions. Increased monokine levels were not present with mononuclear cell cultures stimulated with a T-cell general stimulatory agent or with purified monocytes not specifically stimulated. With endotoxin-stimulated monocytes under in vitro conditions, an increased supernatant was shown for TNF-alpha, but not IL-6. With serum from the different patients cultured with monocytes employed from a healthy control, no difference between the groups was shown in the IL-6 and TNF-alpha response to endotoxin stimulation. The differences in IL-1 beta and TNF-alpha, but not IL-6 levels were differentiated statistically from the smoking and alcohol histories of the patients. These findings suggest that the function of monocytes in general, and thus possibly all mononuclear phagocyte system cells in HNSCC patients, are altered.

Topics: Alcoholism; Carcinoma, Squamous Cell; Cell Movement; Concanavalin A; Head and Neck Neoplasms; Humans; Interleukin-1; Interleukin-12; Interleukin-6; Leukocytes, Mononuclear; Male; Personality Inventory; Retrospective Studies; Smoking; Tobacco Use Disorder; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

The in vitro responsiveness of peripheral blood mononuclear cells (PBMC) T lymphocytes was studied in 81 patients with limited or extended head and neck squamous cell carcinoma (HNSCC), as judged by T, N and T + N stages. Patients included in the study were males below 80 years of age, without auto-immune disease or cachexia, who were not taking any immuno-active medication at the time of diagnosis. The patients were divided into groups according to TNM stage T0-2 vs T3-4, N0-1 vs N2-3 or T + N0-3 vs T + N4-7. When cells from patients with early and late stage, according to T, N or T + N stage, were compared, we found a decreased level of mitogen stimulated T-cells and decreased spontaneous proliferation with increasing disease stage. The same was true if the in vitro mitogenesis of T-cells was analysed separately, depending on the laryngeal or oral cavity/pharyngeal origin of the patients' tumours. If the patients were divided into two groups based on N stage, decreased gamma-interferon, and to some extent interleukin (IL-2), but not IL-4 levels, were found to be related to the disease stage.

Topics: Aged; Analysis of Variance; Carcinoma, Squamous Cell; Cell Division; Concanavalin A; Head and Neck Neoplasms; Humans; Interferon-gamma; Interleukin-2; Interleukin-4; Laryngeal Neoplasms; Lymphocyte Activation; Male; Mitogens; Mouth Neoplasms; Multivariate Analysis; Neoplasm Staging; Pharyngeal Neoplasms; T-Lymphocytes

Immunosuppression in patients with head and neck cancer is well recognized. Previous investigations have demonstrated graded immunosuppression that becomes more pronounced as lymphocyte activity is measured closer to the primary neoplasm. In fresh tumors, a soluble factor has been identified that may partly account for the observed graded immunosuppression.. To examine the effect of soluble factors produced by head and neck sqamous cell carcinoma cell lines on the generation of lymphokine activated killer cell cytotoxicity and peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin.. Conditioned supernatant fluids were generated in a 4-day incubation period, using 5 head and neck squamous cell carcinoma cell lines, and were assayed for the ability to inhibit the generation of lymphokine activated killer cell cytotoxicity and naive peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin.. All conditioned supernatant fluids significantly inhibited the generation of lymphokine activated killer cell cytotoxicity relative to controls, and this inhibition was dose dependent. In contrast, supernatant fluids from a myelogenous leukemic tumor cell line, K562, and an ovarian epithelial cell line, SKOV-3, failed to inhibit cytotoxicity. Supernatant fluids conditioned with head and neck squamous cell carcinoma cell lines also profoundly inhibited the naive peripheral blood lymphocyte proliferation induced by interleukin 2, concanavalin A, and phytohemagglutinin.. These studies demonstrate that the cell lines of head and neck squamous cell carcinoma produce soluble factors that inhibit lymphocyte function. Furthermore, these experiments suggest that the inhibition previously observed with enzymatically disaggregated fresh tumors is due to factors produced by the tumor cells rather than by other cells within the tumor matrix.

Topics: Biological Factors; Carcinoma, Squamous Cell; Concanavalin A; Culture Media, Conditioned; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Head and Neck Neoplasms; Humans; Immune Tolerance; Interleukin-2; Killer Cells, Lymphokine-Activated; Phytohemagglutinins; Tumor Cells, Cultured

An in vitro cytotoxic screening of extracts of Rhaphidophora korthalsii indicated cytotoxicity in the ether fraction. ED50 values of the extract against P388, Molt 4, KB and SW 620 were 12, 14, 8 and 13 micrograms/ml, respectively. The extract was relatively more toxic on P388 and Molt 4 cell lines at concentrations of 50 micrograms/ml and 100 micrograms/ml. Screening with mouse splenocytes showed that the hot water extract had splenocytes stimulating activity.

Topics: Adenocarcinoma; Adjuvants, Immunologic; Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Squamous Cell; Cell Division; Colonic Neoplasms; Coloring Agents; Concanavalin A; Dose-Response Relationship, Drug; Female; Humans; Leukemia; Leukemia P388; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Nasopharyngeal Neoplasms; Plant Extracts; Plant Lectins; Plants, Medicinal; Spleen; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured; Water

A xenogeneic human head and neck squamous cell carcinoma (HNSCC) model in immunocompetent mice was evaluated for its requirement of cyclosporine for progressive tumor growth. Tumor growth and T cell functions were assessed in mice receiving cyclosporine treatment for various lengths of time. Tumor cells were injected s.c. on day 1 and cyclosporine was injected i.p. daily on days 1, 1-7, 1-14, 1-21, or for the entire 28 days of tumor growth. All mice developed tumors. These tumors were confirmed to be squamous carcinomas of human origin histologically and by positive staining for human MHC class I antigen expression. Tumors were largest in mice that received cyclosporine for days 1-21 or days 1-28. Increased tumor size was associated with increased serum levels of tumor-reactive antibodies, an increased intratumoral frequency of CD4+ and CD8+ cells, but a diminished production of interleukin-2 (IL-2) by the tumor infiltrate. Also correlating with increasing tumor size was splenomegaly, a decline in the frequency, but not the absolute levels, of splenic CD4+ and CD8+ cells, and a diminished capacity to proliferate in response to concanavalin A and to be stimulated to secrete IL-2. The HNSCC tumors contributed to the immune decline since T cell functions were more depressed in the tumor bearers than in control mice receiving only cyclosporine treatment. These results demonstrate that human HNSCC tumor xenografts can grow in mice even with limited cyclosporine treatment, and that the survival of these xenografts may, in part, be due to a tumor-induced decline in select T cell functions.

Topics: Animals; Antibodies, Neoplasm; Carcinoma, Squamous Cell; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Concanavalin A; Culture Media, Conditioned; Cyclosporine; Female; Graft Survival; Immunocompromised Host; Interleukin-2; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Pharyngeal Neoplasms; Splenomegaly; Transplantation, Heterologous

Treatment of squamous cell carcinoma (SCCVII) bearing mice with the immunostimulant schizophyllan (SPG) raised the relative content of Mac-1 positive host cells infiltrating the tumor and increased photofrin retention in these tumors. In vitro colony formation assay following photofrin-based photodynamic therapy (PDT) in vivo revealed a greater killing of tumor cells in the SPG pre-treated group, particularly pronounced when the tumor excision was delayed for 8 h after PDT. The tumor cure rate increased approximately three times when PDT was preceded by the SPG therapy. In contrast, the administration of SPG after PDT was of no benefit for tumor control.

Topics: Animals; Carcinoma, Squamous Cell; Cell Death; Cell Migration Inhibition; Clone Cells; Combined Modality Therapy; Concanavalin A; Cytokines; Disease Models, Animal; Female; Hematoporphyrin Derivative; Immunotherapy; Leukocytes; Lung Neoplasms; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Neoplasm Recurrence, Local; Neoplasm Transplantation; Photochemotherapy; Sizofiran; Tumor Cells, Cultured

The binding pattern of two lectins, concanavalin A (ConA) and peanut agglutin (PNA), in various phases of tumour progression in the oral epithelium was studied. These included non-dysplastic, dysplastic and neoplastic lesions as well as normal tissue. ConA and PNA showed intense staining in the basement membrane of all types of lesions. Little difference was observed in the staining patterns between different stages of oral carcinogenesis, either with ConA or PNA. ConA showed mild cytoplasmic and membrane staining in all types of lesions while PNA showed moderate to intense staining in both the cytoplasm and membrane of lower-layer cells in all histological groups. The present study therefore shows that these lectins have limited value in the elucidation of oral carcinogenesis and are of insignificant diagnostic value.

Topics: Carcinoma; Carcinoma, Papillary; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Concanavalin A; Glycoconjugates; Humans; Lectins; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms; Neoplasm Proteins; Peanut Agglutinin; Protein Binding

Three separate processes may contribute to rapid beta-adrenergic receptor desensitization: functional uncoupling from the stimulatory guanine nucleotide-binding protein Gs, mediated by phosphorylation of the receptors by two distinct kinases, the specific beta-adrenergic receptor kinase (beta ARK) and the cyclic AMP-dependent protein kinase A (PKA), as well as a spatial uncoupling via sequestration of the receptors away from the cell surface. To evaluate the relative importance and potential role of the various processes in different physiological situations, a kinetic analysis of these three mechanisms was performed in permeabilized A431 epidermoid carcinoma cells. To allow a separate analysis of each mechanism, inhibitors of the various desensitization mechanisms were used: heparin to inhibit beta ARK, the PKA inhibitor peptide PKI to inhibit PKA, and concanavalin A treatment to prevent sequestration. Isoproterenol-induced phosphorylation of beta 2 receptors in these cells by beta ARK occurred with a t1/2 of less than 20 sec, whereas phosphorylation by PKA had a t1/2 of about 2 min. Similarly, beta ARK-mediated desensitization of the receptors proceeded with a t1/2 of less than 15 sec, and PKA-mediated desensitization with a t1/2 of about 3.5 min. Maximal desensitization mediated by the two kinases corresponded to a reduction of the signal-transduction capacity of the receptor/adenylyl cyclase system by about 60% in the case of beta ARK and by about 40% in the case of PKA. Receptor sequestration was much slower (t1/2 of about 10 min) and involved no more than 30% of the cell surface receptors. It is concluded that beta ARK-mediated phosphorylation is the most rapid and quantitatively most important factor contributing to the rapid desensitization. This rapidity of the beta ARK-mediated mechanism makes it particularly well suited to regulate beta-adrenergic receptor function in rapidly changing environments such as the synaptic cleft.

Topics: beta-Adrenergic Receptor Kinases; Carcinoma, Squamous Cell; Cell Line; Cell Membrane Permeability; Concanavalin A; Cyclic AMP-Dependent Protein Kinases; GTP-Binding Proteins; Humans; Isoproterenol; Kinetics; Protein Kinases; Receptors, Adrenergic, beta

Glycoproteins from normal and malignant human cervix were studied using an organ culture system and compared by gel electrophoresis and autoradiography. Five glycoproteins of 178 kDa, 95 kDa, 93 kDa, 82 kDa and 38 kDa and 1 glycolipid (46 kDa) were detected more frequently in squamous carcinomas. Certain glycoproteins were shown to be oncofoetal and some had affinity for Concanavalin A (Con A). The 82 kDa glycoprotein was present in 16/17 squamous carcinomas but in only 1/13 normal cervices. This band represented a glycoprotein containing glucosamine, mannose, small quantities of methionine and no fucose. These preliminary results suggest that these glycoproteins and in particular the 82-kDa glycoprotein are worthy of further investigation and characterisation.

Topics: Adenocarcinoma; Adult; Aged; Biopsy; Blotting, Western; Carcinoma, Squamous Cell; Chromatography; Concanavalin A; Electrophoresis, Polyacrylamide Gel; Female; Glycoproteins; Humans; Lectins; Middle Aged; Tumor Cells, Cultured; Uterine Cervical Neoplasms

The AIMS/GRXII cell line is a product of the line of research our laboratory is pursuing to understand the response of target cells to sustained hormonal stimulation, a situation simulating the one that brings about in vivo tumorigenesis. The cell line was derived from goat ovarian granulosa cells subjected to luteinizing hormone stress (high doses repeated). It was found to be contact-inhibited, nontumorigenic and secreted progesterone. The majority of cells at any given passage showed hypodiploidy. The cell line required hormonal support till passage 8 after which it was hormone-independent. Thus, the system offers a phase-wise development of the cell line which might be useful in cancer research, particularly to understand the mechanisms of cell transformation at the cellular and molecular level and possible hormone (onco)gene nexus in cell proliferation.

Topics: Animals; Carcinoma, Squamous Cell; Cell Aggregation; Cell Communication; Cell Division; Cell Line; Concanavalin A; Cricetinae; Dose-Response Relationship, Drug; Female; Goats; Granulosa Cells; Humans; Luteinizing Hormone; Mice; Ploidies; Progesterone

Patients with head and neck cancer often have decreased local or regional immunocompetence. Lymphocytes obtained from tumor-involved or -uninvolved lymph nodes (LNL) of these patients showed low or undetectable levels of antitumor cytotoxicity and low proliferative responses in vitro to interleukin 2 (IL2) or mitogens in comparison to peripheral blood lymphocytes (PBL). Lymphokine-activated killer (LAK) cell activity of LNL was lower (P less than 0.05) than that of autologous PBL. Fresh LNL were neither enriched in cells with the CD8+ CD11b+ "suppressor" phenotype nor did they suppress proliferative or cytotoxic responses of autologous PBL in mixing experiments. LNL did not inhibit LAK cell generation from autologous PBL in the presence of IL2. Also, no evidence for the inhibition of autotumor-restricted responses by IL2-activated LNL was obtained. Spontaneous or in vitro-induced production of IL1 beta. TNF alpha, and IFN-tau was low or undetectable in LNL from tumor-involved and -uninvolved lymph nodes in comparison to that in normal or autologous PBL. Mitogen-induced IL2 production was normal in LNL. The depressed ability to produce certain cytokines may be in part responsible for a state of unresponsiveness present in lymph nodes obtained from patients with head and neck cancer. No evidence for the presence of lymphoid suppressor cell in LNL of these patients was obtained.

Topics: Aged; Carcinoma, Squamous Cell; Concanavalin A; Cytokines; Cytotoxicity, Immunologic; Female; Head and Neck Neoplasms; Humans; Immunophenotyping; Interleukin-2; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Lymph Nodes; Lymphatic Metastasis; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes, Regulatory

Exposure of beta-adrenergic receptors (beta ARs) to agonists causes rapid desensitization of the receptor-stimulated adenylyl cyclase response. Three main mechanisms have been implicated in this process: phosphorylation of the receptors by the cAMP-dependent protein kinase (PKA), phosphorylation by the specific agonist-dependent beta AR kinase, and sequestration of the receptors away from the cell surface. By applying inhibitors of these processes to digitonin-permeabilized A431 cells we investigated their contributions to beta AR desensitization. Each process could be selectively inhibited: PKA-dependent phosphorylation by an inhibitor peptide (amino acids 1-24 of the heat-stable inhibitor of PKA (PKI], beta AR kinase-dependent phosphorylation by heparin, and sequestration by concanavalin A. In permeabilized cells, heparin plus PKI completely blocked agonist-induced phosphorylation of the beta ARs. Desensitization was assessed by quantitating the signal transduction efficacy of the system. At high agonist concentrations (approximately 1 microM) up to 70% desensitization occurred. Complete blockade of this desensitization required the concurrent inhibition of all three pathways. When individual pathways were blocked it could be demonstrated that either the PKA or beta AR kinase mechanisms alone resulted in 40-50% desensitization whereas sequestration alone caused 20-30% desensitization. At low agonist concentrations (approximately 10 nM), the PKA pathway was selectively activated. These data indicate that while desensitization mediated via the three different mechanisms can occur independently, the quantitative contributions are not additive. Such findings suggest distinct but overlapping physiological roles for each mechanism in controlling receptor function.

Topics: Adenylyl Cyclases; Carcinoma, Squamous Cell; Carrier Proteins; Cell Line; Cell Membrane Permeability; Concanavalin A; Enzyme Inhibitors; Heparin; Humans; Intracellular Signaling Peptides and Proteins; Isoproterenol; Kinetics; Magnesium; Peptides; Receptors, Adrenergic, beta

Cell-to-cell contact between macrophages and tumor cells is an important initial reaction in a host defense mechanism against tumor cells. The authors have studied cell surface components of human esophageal carcinoma cells recognized by macrophages. Superoxide release from THP-1 cells, a human macrophage cell line, was analyzed in their interaction with a battery of human squamous cell carcinoma cell lines (TE) originated from esophageal cancer patients. The macrophage-triggering ability of TE 1 cell line, a high stimulant, was reduced after treatment with trypsin or tunicamycin, an inhibitor of N-glycosidic glycosylation. Addition of monosaccharides was efficient in competitive inhibition of these cellular interaction. Moreover, con-A-resistant mutation of TE 1 cells was found to reduce their macrophage-triggering ability, associated with increase of L-PHA-binding capacity, suggesting substitution to the GlcNAc beta(1----6)-linked lactosamine antenna in N-glycosidic carbohydrates. These findings suggest that terminal residues of N-glycosidic carbohydrates on some esophageal carcinoma cells may contribute to the recognition sites of macrophages.

Topics: Carcinoma, Squamous Cell; Cell Communication; Cell Division; Cell Membrane; Concanavalin A; Electrophoresis, Polyacrylamide Gel; Esophageal Neoplasms; Glycosides; Humans; Macrophages; Monosaccharides; Phytohemagglutinins; Superoxides; Trypsin; Tumor Cells, Cultured; Tunicamycin

118 surgical specimens were obtained from patients with lung cancer treated in our hospital during the period of 1977-1983 and tested with carcinoembryonic antigen (CEA), ABO (H) isoantigen and Concanavalin A (ConA). The results showed that the CEA assessment, which give no prognostic significance for long-term survival (P greater than 0.05), would be useful in predicting short-term (6 month) out come (P less than 0.05). All patients with positive ABO (H) test for squamous cell lung carcinoma survived at the end of five years. As for ConA, no definite link has been found with the prognosis.

Topics: ABO Blood-Group System; Adenocarcinoma; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Concanavalin A; Humans; Isoantigens; Lung Neoplasms; Prognosis

Lectin-binding sites in clear cell acanthoma (CCA) were studied using an avidin-biotin complex (ABC) with 9 lectins. Formaldehyde-fixed, paraffin-embedded sections of 7 CCA lesions were employed. Positive stainings, similar to those seen in normal epidermis, were observed on the cell surface in CCA with Ricinus communis agglutinin I (RCA-I), Ricinus communis agglutinin II (RCA-II), and wheat germ agglutinin (WGA). Reduced reactivities were observed with Concanavalin A (ConA) and peanut agglutinin (PNA) in CCA. In some areas of CCA lesions, faint stainings were seen with Ulex europaeus agglutinin I (UEA-I). Capability of staining with soybean agglutinin (SBA) was completely lost in the lesions. With Bandeiraea simplicifolia agglutinin II (BSA-II), cytoplasmic stain was seen in a part of upper and spinous layers in CCA lesions. Dolichos biflorus agglutinin (DBA) did not bind to either CCA or normal epidermis. These results indicate that the lectin-binding sites of proliferating cells of CCA resemble those of epidermal keratinocytes and suggest that CCA is a tumor of epidermal origin.

Topics: Aged; Carcinoma, Squamous Cell; Concanavalin A; Female; Glycoconjugates; Histocytochemistry; Humans; Lectins; Male; Middle Aged; Peanut Agglutinin; Plant Lectins; Receptors, Mitogen; Serum Albumin, Bovine; Skin Neoplasms; Soybean Proteins; Wheat Germ Agglutinins

Con A acceptor glycoproteins were analyzed by 2D-PAGE and 125I-Con A overlay in three squamous carcinoma cell lines and compared with those in the simian virus (SV40)-transformed keratinocyte cell line SVK-14 and in normal keratinocytes. The majority of the glycoproteins identified by this technique were expressed at similar levels in all of the cells examined, independent of the culture conditions used. A cell surface glycoprotein gp34 (MW 34 kDa, pI 5.1) was increased in the tumor cells compared with normal keratinocytes and expression varied with the culture density. Another glycoprotein, gp21 (MW 21 kDa, pI 6.3), was found to be increased in expression in normal keratinocytes and stratified hyperconfluent cultures of squamous carcinoma cell lines. This paper describes the potential of this technique to identify membrane glycoproteins which may be expressed as a function of proliferation or differentiation.

Topics: Carcinoma, Squamous Cell; Cell Line; Concanavalin A; Electrophoresis, Gel, Two-Dimensional; Humans; Keratins; Membrane Glycoproteins; Molecular Weight; Reference Values; Skin; Skin Neoplasms; Tumor Cells, Cultured

The distribution pattern of certain monosaccharides in the epithelial cells of the hamster buccal pouch was studied during carcinoma development induced by 9,10-dimethyl-1,2-benzathrancene (DMBA). An avidin-biotin-peroxidase complex (ABC) immunohistochemical technique with high affinity biotinylated lectins was employed to identify monosaccharides. Lectins used in this experiment included Concanavalin A (Con A), for identifying mannose or glucose, Ricinus communis agglutinin I(RCA-I), for identifying galactose, and Ulex europaeus agglutinin I(UEA-I), for identifying fucose. The results show that in normal buccal pouch epithelial cells, fuctose or galactose were concentrated predominantly on the cellular membrane, while mannose and glucose were distributed in the cytoplasm. In the epithelial cells undergoing neoplastic transformation induced by DMBA, most cells showed decreased staining of the above-mentioned monosaccharides, while in other areas the cells were heavily stained. However, the most striking change which occurred was that galactose and fucose shifted from the cellular membrane to the intracytoplasmic area during the malignant transformation. Thus, the changes of anatomic location and intensity of staining of monosaccharides in the buccal pouch epithelium may be used as a criteria for early histochemical diagnosis of malignant transformation.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinoma, Squamous Cell; Concanavalin A; Cricetinae; Epithelium; Immunoenzyme Techniques; Immunohistochemistry; Lectins; Male; Mouth Mucosa; Mouth Neoplasms; Plant Lectins; Receptors, Mitogen

The freshly separated indicator cells (suspension of leukocytes) used in humoral leukocyte adherence inhibition test were labeled either with 14C-amino acid mixture or 3H-concanavalin A (3H-ConA). Instead of counting the adherent cells, the amount of 'adherent' radioactivity was measured by a liquid scintillation spectrometer. By the modified method, sera from 25 lung-carcinoma-bearing patients as well as serum samples from 21 healthy persons were examined in the presence of crude antigens prepared from 'normal' lung tissue or lung tumors of various histologic types. Although the results demonstrated high specificity and reproducibility of both methods, the binding of 3H-ConA to the surface of adherent cells is more expressed and assures higher levels of radioactivity.

Topics: Adenocarcinoma; Adult; Aged; Amino Acids; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Concanavalin A; Female; Humans; Immunologic Techniques; Indicators and Reagents; Leukocyte Adherence Inhibition Test; Lung Neoplasms; Male; Middle Aged

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

Altered cellular immunity in patients with advanced head and neck cancer includes impairments in lymphokine production, blastogenesis, in vitro cytotoxicity, and T-cell levels. Recent evidence for the potential importance of in lymphokine interleukin 2 (IL-2) in patients with cancer prompted a study of the kinetics of IL-2 receptor expression on lymphocytes from patients with untreated advanced head and neck cancer and normal subjects and an evaluation of the in vitro effects of the T-cell immune-reconstituting peptide, thymosin alpha 1. Concanavalin A-stimulated IL-2 receptor expression was maximal after 72 hours and was higher in normal subjects than in patients. This was due to lower levels of helper/inducer (CD4) cells expressing IL-2 receptors in the patients compared with the normal subjects. Thymosin alpha 1 further decreased levels of IL-2 receptor-positive (both CD4 and CD8) cells at 48 and at 72 hours. At 96 hours, levels of IL-2 receptor-positive cells and proportions of cells in G2 and M phases of the cell cycle were similar among both groups of subjects. Simultaneous cell kinetic studies indicated that thymosin alpha 1 down regulation of IL-2 receptors was not due to an effect on proliferation and that differences in IL-2 receptor expression at 72 hours among normal subjects and the patients with cancer were more likely related to differences in cell proliferation kinetics.

Topics: Carcinoma, Squamous Cell; CD4 Antigens; Concanavalin A; Down-Regulation; Flow Cytometry; Head and Neck Neoplasms; Humans; Kinetics; Receptors, Interleukin-2; Thymosin

Manoalide is a marine natural product that has anti-inflammatory and anti-proliferative activities and is an irreversible inhibitor of phospholipase A2 and phospholipase C. It is now shown that the compound is a potent inhibitor of Ca2+ mobilization in several cell types. In A431 cells the increase in epidermal growth factor receptor-mediated Ca2+ entry and release from intracellular Ca2+ stores were blocked by manoalide in a time-dependent manner with an IC50 of 0.4 microM. The effect of manoalide on phosphoinositide metabolism, namely the production of inositol monophosphate, did not coincide with its effect on the epidermal growth factor response. In GH# cells, manoalide blocked the thyrotropin-releasing hormone-dependent release of Ca2+ from intracellular stores without inhibition of the formation of inositol phosphates from phosphatidylinositol 4,5-bisphosphate. Manoalide also blocked the K+ depolarization-activated Ca2+ channel in these cells as well as the activation of the channel by Bay K8644 with an IC50 of 1 microM. In addition, manoalide also inhibited the Ca2+ influx induced by concanavalin A in mouse spleen cells in a time- and temperature-sensitive manner with an IC50 of 0.07 microM. However, neither forskolin-activated adenylate cyclase in A431 cells nor the distribution of the potential sensitive dye, 3,3'-dipropylthiodicarbocyanide iodide in GH3 cells was affected by manoalide. Thus, manoalide acts as a Ca2+ channel inhibitor in all cells examined. This action may account for its effects on inflammation and proliferation and may be independent of its effect on phospholipases.

Topics: Animals; Calcium; Calcium Channel Blockers; Carcinoma, Squamous Cell; Cell Line; Colforsin; Concanavalin A; Cyclic AMP; Epidermal Growth Factor; Humans; Inositol Phosphates; Ion Channels; Kinetics; Lymphocytes; Mice; Terpenes

A number of peptide growth factors have been shown to induce the secretion of type I collagenase into the medium of human fibroblast cultures (Chua et al., 1985). In this study the ability of eye-derived growth factor, lectin and tumor-promoting agents on collagenase induction in human fibroblast cells were examined. These agents were found to be able to induce collagenase production to a similar extent as epidermal growth factor. Dexamethasone at 10-100 nM was found to suppress collagenase induction in human fibroblast cells. The cell-type specificity of this enzyme induction by growth factors was studied by using a human epidermoid carcinoma cell line, A-431. An Mr 55,000 band appeared in the medium of A-431 cells upon 22 h exposure to EGF. Two-dimensional peptide pattern of the Mr 55,000 band in A-431 cells was identical to the counterpart in HF cells. Our results indicated that the induction of collagenase was not unique to human fibroblast cultures.

Topics: Carcinoma, Squamous Cell; Cell Line; Concanavalin A; Dexamethasone; Epidermal Growth Factor; Fibroblast Growth Factors; Fibroblasts; Growth Substances; Humans; Microbial Collagenase; Molecular Weight; Ocular Physiological Phenomena; Tetradecanoylphorbol Acetate

Human squamous carcinoma (COLO-16) cells release factors which specifically stimulate the synthesis of major acute-phase plasma proteins in human and rodent hepatic cells. Anion exchange, hydroxyapatite, lectin, and gel chromatography of conditioned medium of COLO-16 cells result in separation into three distinct forms of hepatocyte-stimulating factors (designated HSF-I, HSF-II, and HSF-III) with apparent molecular weights of 30,000, 50,000 and 70,000, respectively. None of the preparations contains detectable amounts of thymocyte-stimulating activity. Each of the three HSF forms stimulates the accumulation of mRNA for alpha 1-antichymotrypsin in the human hepatoma cell line, HepG2. When the same factors were added to primary cultures of adult rat hepatocytes, the expression of the same set of plasma proteins was modulated as by nonfractionated medium. The hormonally induced accumulation of mRNA for acute phase proteins is qualitatively comparable to that occurring in the liver of inflamed rats. Unlike in human cells, in rat liver cells dexamethasone acts additively and synergistically with HSFs. The only functional difference between the three HSF forms lies in the level of maximal stimulation. HSF-I represents the predominant form produced by normal human keratinocytes and closely resembles in molecular size and isoelectric point the activity produced by activated peripheral blood monocytes while the larger molecular weight forms are more prevalent in human as well as mouse squamous carcinoma cells. The observation that HSFs from different sources elicit essentially the same pleiotropic response in hepatic cells led to the hypothesis that the species-specific reaction of adult liver cells to inflammatory stimuli is pre-programmed and that the function of any HSF is to trigger and tune the execution of this fixed cellular process.

Topics: alpha 1-Antichymotrypsin; alpha-Macroglobulins; Animals; Carcinoma, Squamous Cell; Cells, Cultured; Chymotrypsin; Concanavalin A; Fibrinogen; Humans; Interleukin-1; Interleukin-6; Isoelectric Point; Liver; Liver Neoplasms, Experimental; Molecular Weight; Orosomucoid; Proteins; Rats; RNA, Messenger

Seventy-six skin biopsies of proliferative lesions were studied by using 4 different lectins and an avidin-biotin-peroxidase complex. In solar keratosis, Bowen's disease and squamous cell carcinoma, malignant-appearing keratinocytes exhibited loss of membrane staining with Concanavalia ensiformis agglutinin (Con A), but revealed cytoplasmic staining. When incubated with peanut agglutinin (PNA), the malignant keratinocytes did not stain. However, the PNA binding sites were not absent, but masked by sialic acid. Following cleavage of the sialic acid with neuraminidase, free PNA binding sites could be demonstrated in the plasma membranes. In contrast, the keratinocytes in keratoacanthomas showed membrane staining with Con A and also contained free PNA binding sites. These histochemical findings confirm and extend our earlier observations regarding cell surface carbohydrates in premalignant and malignant epidermal lesions.

Topics: ABO Blood-Group System; Binding Sites; Bowen's Disease; Carbohydrate Metabolism; Carcinoma, Squamous Cell; Cell Membrane; Concanavalin A; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Keratosis; Lectins; Neuraminic Acids; Peanut Agglutinin; Plant Lectins; Skin; Skin Neoplasms; Sunlight; Wheat Germ Agglutinins

Serum concentrations of serum amyloid A protein (SAA), peripheral blood lymphocytes (PBL) mitogenic response to phytohemagglutinin (PHA) and Concanavalin A (Con A), numbers of circulating T- and B-lymphocytes and length of survival after diagnosis were measured in 50 patients with cancer of the lung. SAA levels were significantly elevated when compared to 50 control subjects (P less than 0.001), but did not correlate with state of tumor spread at the time of diagnosis. Mitogenic responses of PBL from the cancer patients to PHA and Con A were significantly depressed (P less than 0.001), but also did not predict state of metastatic spread. The percentage of circulating T-lymphocytes was also significantly depressed in cancer patients when compared to controls. In six patients who survived tumor-free for greater than 2.5 years, SAA serum concentrations returned to normal. Statistical analysis showed a significant correlation between SAA serum concentrations and PBL mitogenic response to Con A. In addition, both high SAA concentrations and depressed PBL responses to Con A correlated with shortened survival. Therefore, these parameters may be of value in evaluating prognosis in patients with lung cancer. In addition, serial monitoring of SAA concentrations may be of value in evaluating recurrence or cure of lung cancer.

Topics: Adenocarcinoma; Adult; Aged; Amyloid; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cells, Cultured; Concanavalin A; Humans; Leukocyte Count; Lung Neoplasms; Lymphocytes; Male; Middle Aged; Phytohemagglutinins; Prognosis; Prospective Studies; Serum Amyloid A Protein

Lymphocyte stimulation with Con A and specific immune reactivity to BCG (antibody formation to BCG and DTH reaction to PPD) were determined in BCG-treated, surgically treated and untreated cows with ocular squamous cell carcinoma. In tumor-bearing cows the Con A-induced proliferation of lymphocytes was reduced when compared to healthy controls. This suppression consisted of a reduced blastogenic response to Con A of lymphocytes from tumor-bearing cows, and the presence of a factor in the sera of these animals, as these sera suppressed the blastogenic response of lymphocytes from healthy cows. BCG had only a minor influence on the suppressive activity. Antibodies to BCG were demonstrated in 50% of the BCG-treated animals. The formation of antibodies was not influenced by intradermal injection of PPD of Mycobacterium bovis. Absorption of a BCG antibody containing serum with BOSCC tumor extracts did not reveal the existence of cross reacting antigens between BCG and BOSCC. Pretherapeutic and posttherapeutic Con A reactivity could not be correlated with clinical response. Of the 30 BCG treated cows 29 developed a positive DTH reaction to PPD. Correlation between clinical response and immune reactivity was seen only with regard to the DTH reaction to PPD: this reaction remained positive for a longer period after treatment in animals with a favorable clinical outcome than in nonresponding animals.

Topics: Animals; Antibodies, Bacterial; BCG Vaccine; Carcinoma, Squamous Cell; Cattle; Cattle Diseases; Concanavalin A; Eye Neoplasms; Female; Hypersensitivity, Delayed; Lymphocyte Activation; Suppressor Factors, Immunologic; Tuberculin

To evaluate the efficacies of various administration routes of the streptococcal preparation, OK-432, we studied the lymphocyte proliferation responses to lectins in patients with malignancies. OK-432 was administered intravenously (I.V.), intramuscularly (I. M.) or intradermally (I.D.) for 2 weeks. Lymphocyte proliferation responses to concanavalin A, PHA and SuM (crude extract of OK-432) were studied before and after OK-432 administration. Enhanced responses were observed in 7 out of 9 patients (77.8%) in the I.V. group compared with 3 out of 7 (44.2%) in the I.M. group and 4 out of 9 (44.4%) in the I.D. group. Ratios of stimulation index (S.I.) after administration over S.I. before administration were highest in the I.V. group. These results suggest that I.V. administration of OK-432 is most effective for stimulating host immune systems.

Topics: Adenocarcinoma; Adult; Aged; Biological Products; Carcinoma, Squamous Cell; Concanavalin A; Female; Humans; Infusions, Parenteral; Lung Neoplasms; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Picibanil

For the detection of cancerous and precancerous lesions in cervical cytopathology, the feasibility of a concanavalin A-peroxidase labeling procedure was tested and compared with the Papanicolaou method. To this end, the percentage of labeled flattened epithelial cells with a morphologically normal appearance present in cervical cell suspensions was determined. It was found that the mean labeling percentage of the control group was 71% (SD, 11%). The means for mild, moderate, and severe dysplasia groups were, respectively, 54% (SD, 19%), 48% (SD, 13%), and 44% (SD, 16%). The mean for the carcinoma in situ group was 32% (SD,11%), and for the squamous cell carcinoma group 16% (SD, 5%). It appeared that the labeling percentage gradually decreases with increasing atypia of the epithelium as confirmed by histological observation. A complete dissimilarity was found between healthy individuals and cancer patients. In a follow-up study it was found that the mean labeling percentage did not alter in cases of an unchanged stage of disease. A reestablishment of the normal concanavalin A-peroxidase labeling percentage often appeared once the cancerous or precancerous lesion was treated. In conclusion, the concanavalin A-peroxidase labeling method can be considered as a supplementary technique to the Papanicolaou method for the early detection of cervical cancer. It reduces the effect of sampling and screening errors of the Papanicolaou method, and it allows a more objective cytological diagnosis. In addition, it may possess prognostic significance.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Adhesion; Concanavalin A; Female; Horseradish Peroxidase; Humans; Precancerous Conditions; Uterine Cervical Neoplasms

The effects of cyclosporin A, prostaglandin E1 and indomethacin were studied on lectin-dependent cell-mediated cytotoxicity (LDCC) against adherent HEp-2 human epipharynx carcinoma target cells. LDCC activity by human peripheral blood lymphocytes was evaluated by detachment from the monolayer of [3H]thymidine-prelabelled HEp-2 cells in a 24-h assay at 50:1 effector:target cell ratio in the presence of 25 micrograms/ml concanavalin A. Under these conditions, but without concanavalin A, considerable natural cell-mediated cytotoxicity was not elicited although LDCC was significantly augmented in the presence of concanavalin A. Addition of both cyclosporin A (0.1, 1.0 or 10 micrograms/ml) and prostaglandin E1 (10(-8), 10(-7) or 10(-6) M) dose-dependently suppressed LDCC activity. Indomethacin (0.1, 1.0 or 10 micrograms/ml) did not in itself influence LDCC although suppression of LDCC by cyclosporin A, but not prostaglandin E1, was abrogated in the presence of indomethacin. Similar to indomethacin, acetyl salicylic acid also reversed the inhibition of LDCC by cyclosporin A. In parallel experiments, cyclosporin A elicited a more than two-fold increase of prostaglandin E production under LDCC assay conditions as measured by radioimmunoassay. Contrary to LDCC, depression of concanavalin A induced blastogenesis by cyclosporin A was not influenced by indomethacin, suggesting that the inhibition by cyclosporin A of LDCC and concanavalin A-induced blastogenesis proceed via different mechanisms.

Topics: Carcinoma, Squamous Cell; Cell Line; Concanavalin A; Cyclosporins; Cytotoxicity, Immunologic; Drug Antagonism; Humans; Immunosuppression Therapy; Indomethacin; Lymphocytes; Prostaglandins E; Radioimmunoassay

Con A-stimulated leukocytes previously treated with IFN-alpha (1500 IU/ml for 4 h) were very suitable for the production of IFN-gamma with a high titre even under large-scale conditions. The properties of the IFN produced under such conditions were identical to those of IFN-gamma. The IFN-gamma produced in primed cultures showed two peaks of antiviral activity corresponding to molecular weights of 51 000 and 23 000 daltons.

Topics: Carcinoma, Squamous Cell; Cell Line; Cell Survival; Cells, Cultured; Concanavalin A; Humans; Interferon Type I; Interferon-gamma; Leukocytes; Parainfluenza Virus 1, Human

We have studied some cellular characteristics and the transplantability of a newly induced squamous cell carcinoma, Sq1-SC, in comparison with the ascites-transformed subline of the same tumor, Sq1-AA. We could demonstrate that the AA tumor differed from the SC tumor in the pattern of intravenously induced 'experimental metastases'. The SC tumor preferentially gave rise to extrapulmonary tumor colonies ('metastases'), while the AA tumor exclusively gave rise to lung colonies. Comparison with the ascites tumor growing in solid form subcutaneously (AS tumor) shows that the enzymatic treatment, which is necessary to bring solid tumors into viable and dissociated suspensions, can have a decisive influence on tumor cell lodgement in vessels and metastasis.

Topics: Animals; Ascites; Blood Coagulation; Carcinoma, Squamous Cell; Cell Separation; Concanavalin A; Electrophoresis; Female; Lectins; Methylcholanthrene; Mice; Mice, Inbred CBA; Neoplasm Metastasis; Neoplasm Transplantation; Trypsin; Wheat Germ Agglutinins

The present study suggests a correlation between concanavalin A-driven blastogenesis and the clinical course of head and neck cancer. Blastogenesis assays were conducted on peripheral blood lymphocytes from controls and from patients with squamous cell carcinoma (SCC) of the head and neck. Our results indicated that 3H-thymidine incorporation in response to concanavalin A and phytohemagglutinin stimulation were significantly lower for patients' than for controls' lymphocytes, whereas PWM stimulation was not statistically different in these two groups. Differences between patients and controls were most notable with concanavalin A stimulation. Five of seventeen patients had a response to concanavalin A stimulation that was in the normal range when expressed as relative to control values. The clinical course of these five patients seems to point to a better prognosis than that of the remaining patients who had below-normal mitogenic responses.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Concanavalin A; Female; Head and Neck Neoplasms; Humans; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Phytohemagglutinins; Prognosis

The lectin binding capacity of the cell surface of normal flattened exfoliated epithelial cells of the uterine cervix was investigated looking for differences between specimens from normal and cancer patients. The method used was a modified concanavalin A-horseradish peroxidase (Con A-HRP) labeling procedure. Both normal and cancer specimens contain labeled as well as unlabeled usual flattened cells. There is a distinct difference between the labeling intensity of labeled and that of unlabeled cells. Quantification of the labeling results has been achieved using a light microscope equipped with a computerized video system. Apparently healthy persons, having a percentage of labeled flattened cells between 54 and 94% (mean = 73%, SD = 10%, N = 40), were totally discriminated by this method from the cancer patients. These patients with a histologically confirmed squamous cell carcinoma, showed a labeling percentage between 10 and 22% (mean = 15%, SD = 4%, N = 10). Hormonal factors, such as phase of cycle and pill use, appeared to have no significant influence. Statistical analysis revealed that at least 99% of all healthy persons will have a labeling percentage above 45%, while at most 1% of the cancer patients will show a labeling percentage above 30%. When choosing the labeling percentage of 45% as critical value, the Con A-HRP labeling might serve as an additional detection method for cancer of the uterine cervix. Moreover, as it is based on the abundantly present normal cells, and not on the often scarce abnormal cells, the method is not liable to sampling and screening errors.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Cervix Uteri; Computers; Concanavalin A; Contraceptives, Oral; Epithelial Cells; Epithelium; Female; Horseradish Peroxidase; Humans; Menstrual Cycle; Microscopy; Microscopy, Electron; Middle Aged; Peroxidases; Statistics as Topic; Uterine Cervical Neoplasms

Concanavalin A-peroxidase (Con A-HRP) labeling of exfoliated cells of the uterine cervix have been shown to possess clinical significance in the detection of cancer. In the present study, a more simple method is used instead of the earlier applied complicated method. These two procedures for the assessment of the labeling results are compared. The first method is an objective machine-aided assessment procedure, consisting of a light microscope connected with a video system used in the sliced mode. The second is a more subjective method using human visual assessment with a light microscope only. The latter method would be suitable for routine use, if it shows similar Con A-HRP labeling results as obtained with the machine-aided procedure. In comparison with the machine-aided assessment procedure, the visual assessment procedure is less accurate. Moreover, the visual assessment is accompanied by intraobserver (between day) and interobserver variations. Although the discriminatory capacity in the detection of cancer patients is significantly lower for the human visual assessment procedure, this difference is small. It is of clinical relevance that in general a complete discrimination of healthy individuals and cancer patients is still possible. Therefore, visual assessment with a light microscope only, is preferred because of its simple equipment, which allows this procedure to be used as a routine method.

Topics: Carcinoma, Squamous Cell; Concanavalin A; Female; Horseradish Peroxidase; Humans; Microscopy; Peroxidases; Uterine Cervical Neoplasms; Vaginal Smears

Using the methods described, it is not possible to determine the number of N- and O-linked oligosaccharides on ectopic hCG beta. On standard hCG beta there are two NeuAc residues on each N- and O-linked oligosaccharide, so that the number of NeuAc residues is proportional to the number of oligosaccharides. Ectopic hCG beta and desialylated ectopic hCG beta are of similar molecular size to the standard preparations (gel filtration and RIA with anti-CTP antisera, data not presented). This suggests that ectopic hCG beta is sialylated to a similar extent as standard hCG beta, so the number of oligosaccharides on ectopic hCG beta could be similar to the number on standard hCG beta. There is a Fuc attached to the N-linked oligosaccharides of standard hCG beta (Fig. 3). Using the methods described, it was not possible to determine if this residue is also found on the N-linked oligosaccharides of ectopic hCG beta. Recently, a second form of ectopic hCG beta was identified (22). This form lacks the characteristic hCG beta carboxyterminal peptide, and as such is unrecognized by the RIA used in this study. Like the ectopic hCG beta described herein, and that produced by other cancers, this molecule only partially binds to Con A, and binds to Ricinus communis-120 following neuraminidase digestion. Intact hCG and free hCG subunits, which only partially bind to Con A, are found in cancer tissues, cancer sera, and the medium of cultured trophoblastic and nontrophoblastic cancer cells (Table 1). Our studies with DoT cancer of the cervix cells clearly indicate that the partial binding could be the consequence of the linkage of extra beta G1cNAc residues.

Topics: Carcinoma, Squamous Cell; Cell Line; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Chromatography, Affinity; Concanavalin A; Female; Glycoside Hydrolases; Hormones, Ectopic; Humans; Lectins; Oligosaccharides; Peptide Fragments; Uterine Cervical Neoplasms

The lectin, Concanavalin A(Con A) has been used to localize specific sugar residues (D-glucose, D-mannose and D-fructose) in premalignant lesions and squamous-cell carcinomas induced following cryosurgery of the mouse submandibular gland. The original Con A-horseradish peroxidase (HRP) technique as well as its combination with periodate oxidation and subsequent reduction by borohydrate were used to compare the epithelial elements during submandibular gland carcinogenesis. Granules in the granular convoluted tubule cells which were weakly reactive to the Con A-HRP method were not present in the premalignant duct like structures. The epithelium of premalignant lesions, duct-like structures, multicystic lesions, and squamous-cell carcinomas were positive for the cell-surface and intercellular substances; and basement membranes and stromal fibers were also positive. The results indicated that throughout malignant transformation of the ductal segments, premalignant epithelia lost Con A-HRP-staining granules and that Con A-binding patterns in induced squamous-cell carcinomas were similar to those found in squamous-cell epithelium.

Topics: Animals; Carcinoma, Squamous Cell; Concanavalin A; Male; Mannose; Methylmannosides; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Precancerous Conditions; Receptors, Concanavalin A; Salivary Gland Neoplasms; Submandibular Gland Neoplasms

Kupffer cells from the liver of normal rats were checked for their natural cytostatic capabilities using an in vitro target cell growth inhibition assay. A strong cytostatic effect was observed on an human tumor cell line and was shown to be exerted on various transformed or normal target cells with only small differences in their susceptibility. The inhibition of target cell proliferation was shown to depend on the effector/target cell ratio. Different experimental data suggest that an intimate membranal contact between Kupffer cells and target cells is required.

Topics: Animals; Carcinoma; Carcinoma, Squamous Cell; Cell Cycle; Cell Line; Cells, Cultured; Chick Embryo; Concanavalin A; DNA Replication; Embryo, Mammalian; Fibroblasts; Humans; Kupffer Cells; Liver; Mouth Neoplasms; Rats; Rats, Inbred Strains; Ultraviolet Rays

In earlier experiments chemotactic responsiveness of peripheral blood monocytes obtained from patients with head and neck cancers was found to be markedly depressed. In an attempt to attribute this defect in migration to an influence excited by low molecular weight factors of less than 25,000 daltons, derived from the tumor, Amicon filtrates of head and neck cancer cells were administered subcutaneously to C3H mice 24 hrs. before the intraperitoneal injection of concanavalin A. Subsequent macrophage accumulation into the peritoneal cavity was quantified. A clear inhibition of macrophage infiltration was found, particularly when filtrates of poorly differentiated tumors were used. Injection of filtrates from healthy oral mucosa were negative, whereas mouse mammary carcinoma filtrates strongly inhibited accumulation.

Topics: Adult; Aged; Animals; Carcinoma, Squamous Cell; Cell Extracts; Cell Movement; Concanavalin A; Female; Head and Neck Neoplasms; Humans; Macrophages; Male; Mice; Mice, Inbred C3H; Middle Aged; Molecular Weight; Phytohemagglutinins; Tissue Extracts

The concentration of alpha 1-acid glycoprotein (AGP, orosomucoid) was measured in sera from 19 patients with primary squamous cell carcinoma of the lung, 16 patients with an inflammatory lung disease and 17 persons with normal health. All sera were further subjected to crossed immuno-affinoelectrophoresis with addition of Con A in the first dimension and sugar in the second dimension. The distribution of AGP into four microheterogeneity forms, which were the result of this analysis, was estimated by measuring the area under the precipitation curve. The microheterogeneity patterns of AGP in the three groups were significantly different from each other (p less than 0.001). The total concentration of AGP in the two groups of patients was significantly different from the concentration in the healthy group (p less than 0.001).

Topics: Carcinoma, Squamous Cell; Concanavalin A; Humans; Immunoelectrophoresis, Two-Dimensional; Lung Diseases; Lung Neoplasms; Orosomucoid

The suppressor activity induced by Concanavalin A (Con A) was evaluated in peripheral lymphocytes from 20 patients with solid malignant tumors of different origin, that is: 9 lung epidermoid carcinomas; 6 breast adenocarcinomas and 5 melanomas. Simultaneously 10 normal control subjects were studied. No significant differences in the percentage of suppression were found in patients bearing breast adenocarcinoma and lung epidermoid carcinoma as compared to normal subjects. Melanoma patients, on the contrary, showed significant differences on the same test. On the other hand, the Con A lymphoproliferative response was found to be only significantly increased in the melanoma patients compared to normal controls. No differences were found in the percentage of peripheral blood lymphocytes between patients and controls.

Topics: Adenocarcinoma; Adult; Aged; Breast Neoplasms; Carcinoma, Squamous Cell; Concanavalin A; Humans; In Vitro Techniques; Lung Neoplasms; Lymphocyte Activation; Lymphocytes; Melanoma; Middle Aged; T-Lymphocytes, Regulatory

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

This study is, to our knowledge, the first attempt to evaluate cellular immune mechanisms in regional lymph nodes of patients with head and neck cancer. Twenty lymph nodes from eight patients with stage III-IV squamous cell carcinoma were evaluated using an in vitro culture system. The T-cell mitogenic (concanavalin A) response of patients' peripheral blood mononuclear cells was modulated by the addition of cells from regional lymph nodes removed at neck dissection. Modulatory activity showing augmentation was significantly correlated with the size of the primary tumor and histopathologic grade of the tumor. Modulatory activity did not correlate with the histologic pattern of lymph node reactivity. Although these relationships suggest that regional immunity may be important in tumor-host interactions, further study is necessary to establish their biologic and prognostic importance.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Concanavalin A; Female; Head and Neck Neoplasms; Humans; Immunity, Cellular; In Vitro Techniques; Lymph Nodes; Male; Middle Aged; T-Lymphocytes

Three cell surface parameters of epidermal cells have been studied by immunofluorescence, pemphigus antigens, concanavalin-A binding sugars, and beta 2 microglobulin. Biopsy specimens were taken from a total of 59 patients with psoriasis, seborrheic and solar keratosis, squamous cell carcinoma, and basal cell epithelioma. We found a loss of demonstrability of all parameters in dedifferentiated tumors or tumor areas in squamous cell carcinoma, premonitory changes in solar keratosis, and no changes in seborrheic keratosis. In the psoriatic epidermis a granular redistribution of the cell surface parameters was occasionally observed in circumscribed areas of the epidermis. A selective loss of the demonstrability of beta 2 microglobulin was the prominent feature in basal cell epithelioma. Our findings demonstrate that the alterations of the cell surface differ in malignant and premalignant skin tumors, in basal cell epithelioma, and in benign psoriatic hyperplasia.

Topics: Antigens; beta 2-Microglobulin; Beta-Globulins; Binding Sites; Carcinoma, Squamous Cell; Concanavalin A; Fluorescent Antibody Technique; Humans; Keratosis; Pemphigus; Precancerous Conditions; Psoriasis; Skin Neoplasms

Epidermal growth factor (EGF) receptors extracted with Triton X-100 from human skin fibroblasts and A431 epidermoid carcinoma cells rapidly lose EGF-binding activity precipitable with polyethylene glycol. The presence of concanavalin A which can cross-link and, thereby, aggregate the receptors, allowed quantitative recovery of the lost EGF-binding activity. Scatchard analysis of EGF binding of Triton X-100-solubilized receptors showed that A431 cells and skin fibroblasts possess approximately 1.5 X 10(6) and 7 X 10(4) EGF-binding sites/cell, respectively, which exhibit similar affinities for the ligand. The heavy isotope density-shift method was employed to determine whether differences in rates of receptor synthesis or decay account for the large difference in number of receptors/cell between the two cell types. After shifting cells to medium containing heavy (15N, 13C, and 2H) amino acids, light and heavy receptors, solubilized from total cellular membranes, were resolved by isopycnic banding on density gradients and then quantitated. It was demonstrated that A431 cells synthesize EGF receptors at a rate 12 times faster than skin fibroblasts and that the half-life for receptor decay of A431 cells is somewhat longer (t1/2 = 16 h) than that (t1/2 = 9 h) of fibroblasts. Down-regulation of cell surface and total cellular EGF-binding capacity in A431 cells occurs with a t1/2 of 2-3 h and results in a 70-83% decrease in receptor level in 12 h. Scatchard analysis revealed that these changes in EGF binding were due to an alteration of receptor number and not EGF-binding affinity. Rates of EGF receptor synthesis and inactivation/decay were determined by the heavy isotope density-shift method. No change in the rate of receptor synthesis occurred as a consequence of EGF receptor down-regulation. Down-regulation, however, caused a decrease in receptor half-life from 16 to 4.5 h. These results indicate that EGF-dependent regulation of EGF receptor level in A431 cells involves an alteration of the rate of receptor inactivation.

Topics: Carcinoma, Squamous Cell; Cell Line; Cells, Cultured; Concanavalin A; Epidermal Growth Factor; ErbB Receptors; Fibroblasts; Humans; Kinetics; Molecular Weight; Receptors, Cell Surface; Skin

The effects of the addition of indomethacin to PHA or Con A stimulated lymphocytes from patients with untreated squamous cell carcinoma of the head and neck or from patients with the disease who have just finished irradiation therapy from the disease was quantitated and compared to those of the control group. Lymphocytes from eight of 26 patients with untreated carcinoma were significantly augmented by the addition of indomethacin. The remaining eighteen patients were equal to the controls. For all 17 patients who had just finished extensive field irradiation therapy, significant enhancement of PHA and Con A reactivity by indomethacin was found, which did not appear to be solely a function of low baseline mitogen reactivity. In additional studies, stimulated lymphocytes of irradiated patients were tested for their sensitivity to the inhibitory effect of PGE2. The mitogen treated lymphocytes from all patients that had just finished irradiation therapy were found to be significantly more sensitive to the inhibition by PGE2 as compared to the normal lymphocyte response. This effect was also found not to be related merely to a low PHA or Con A reactivity of the lymphocytes. In both patient groups there was a striking correlation between the percent augmentation of indomethacin and the percent inhibition of PGE2 in that when the percent augmentation values were low so were percent inhibition values and when the degree of augmentation by indomethacin was elevated so was the inhibition by PGE2. This data suggests that increase sensitivity of stimulated lymphocytes to PGE2 may be responsible, at least in part, for the depressed mitogen response and the significant augmentation of this immune response by indomethacin in about 1/3 of the untreated patients with advanced head and neck carcinoma and in those patients who have just finished irradiation therapy. The results of this study support the hypothesis that perhaps patients receiving irradiation therapy may benefit by the oral administration of indomethacin, an approach that needs further consideration.

Topics: Carcinoma, Squamous Cell; Concanavalin A; Head and Neck Neoplasms; Humans; Indomethacin; Lymphocyte Activation; Lymphocytes; Reference Values

The mean number of lymphocytes, response to phytohemagglutinin (PHA), and response to concanavalin A (Con A) in whole-blood cultures for 106 patients with head and neck cancer were 83%, 73%, and 64%, respectively, of values for healthy control individuals. During radiotherapy, lymphocyte counts declined to 44% and PHA and Con A responses declined to about one third of control values. Lymphocyte counts slowly increased after treatment to 77% of control values after two years, but responses to mitogens remained at about 40%. Responses to PHA and Con A for 38 patients who lived beyond 18 months were significantly greater before and after treatment than responses for 39 patients who died within 18 months. In general, a poor pretreatment response to PHA and Con A correlated with a poor clinical course, whereas responses near the control level indicated a good clinical course.

Topics: Carcinoma, Squamous Cell; Concanavalin A; Head and Neck Neoplasms; Humans; Leukocyte Count; Lymphocytes; Neoplasm Staging; Phytohemagglutinins; Pokeweed Mitogens; Prognosis

Two ascites tumors in syngeneic CBA mice are described, viz., MCB 21-AA and MCB 31-AA, with their solid progenitors: A sarcoma (MCB 21-SS) and a squamous cell carcinoma (MCB 31-SC), induced by gastric feeding of 20-methylcholanthrene. The ascites tumor cells have certain characteristics in common, which they do not share with either cells from the solid tumors or even with cells from solid ascites tumors (-21-AS and -31-AS=ascites tumor transplanted s.c.). Presumably some of these differences, for instance, in PAS stainability, electrophoretic mobility and lectin agglutinability, are due to enzyme treatment required to bring solid tumors into suspension. Between the two ascites tumors there are certain differences in cell size, aggregability, and growth rate. They are similar, however, in requiring large cell doses for transplantation in syngeneic animals, which is also true for the solid (SS and SC) tumors. MCB 21 and -AA even required fewer cells for transplantation in allogeneic A mice than in syngeneic CBA mice. MCB 31-AA is also allotransplantable. The pattern of spread, after i.v. cell injection, is almost exclusively to the lungs for all tumor lines.

Topics: Animals; Ascites; Carcinoma, Squamous Cell; Cell Nucleus; Chromosomes; Concanavalin A; Electrophoresis; Fibrosarcoma; Lectins; Methylcholanthrene; Mice; Mice, Inbred CBA; Neoplasm Transplantation; Neoplasms, Experimental; Surface Properties; Transplantation, Homologous; Transplantation, Isogeneic

Cellular immunity of the delayed type in women with intraepithelial carcinoma (carcinoma is situ) of the vulva was investigated by an in vitro assay of mitogen-induced lymphocyte transformations. Test results from 9 patients were compared to those of 23 age-matched control subjects. Lymphocyte transformation responses in counts per minute were significantly lower for women with carcinoma in situ of the vulva than for control subjects for phytohemagglutinin-P (at 50 microgram/ml) 6238 and 28,102 (P less than 0.0001); for phytohemagglutinin-P (at 165 microgram/ml 7222 and 21,417 (P less than 0.001); for concanavallin A, 14,988 and 41,888 (P less than 0.0001); and pokeweed mitogen, 20,861 and 49,601 (P less than 0.001). No significant differences in lymphocyte transformations were noted between these two groups to the specific antigens, Candida or streptokinase-streptodornase. Four patients with carcinoma in situ of the vulva were also found to have intraepithelial carcinoma of the cervix and/or vegina. The occurrence and clinical course of carcinoma in situ of the vulva in some women may be related to an underlying defect in cellular immunity. Immunosuppression may also explain the frequent association noted between carcinoma of the vulva and the development of other malignant neoplasms.

Topics: Adolescent; Adult; Bowen's Disease; Carcinoma in Situ; Carcinoma, Squamous Cell; Concanavalin A; Female; Humans; Immunity, Cellular; Lymphocyte Activation; Phytohemagglutinins; Pokeweed Mitogens; Vulvar Neoplasms

Regional lymph node lymphocytes from patients with squamous cancer of the head and neck were tested in vitro for their ability to proliferate in response to phytohemagglutinin, concanavalin A, and allogeneic stimuli in one-way mixed lymphocyte culture. Their ability to act as cytotoxic effectors in phytohemagglutinin-dependent cellular cytotoxicity was also evaluated, and all results were compared to normal lymph node or blood lymphocytes. The regional lymph node lymphocytes retained proliferative capabilities equal to those in control lymph nodes or blood, whereas they were unable to mediate phytohemagglutinin-dependent cellular cytotoxicity. However, this was not a tumor-related effect because normal lymph node lymphocytes were also ineffective in this assay. The failure of the regional immune response to control early tumor growth could not be accounted for by generalized nonspecific immunosuppression in regional lymph node lymphocytes, inasmuch as these cells demonstrated normal in vitro activity.

Topics: Adult; Aged; Antigens; Carcinoma, Squamous Cell; Concanavalin A; Cytotoxicity Tests, Immunologic; Head and Neck Neoplasms; Humans; Immunity; Immunity, Cellular; Kinetics; Lectins; Lymph Nodes; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Middle Aged; T-Lymphocytes

Patients with mucosal squamous cell carcinoma of the head and neck generally have suppressed T cell function, and this suppression tends to be more pronounced with progression of disease. The prognostic relationships of multiple tests of immune function were analyzed in 183 clinically staged patients. Correlation of immune parameters with prognosis was evident only with the DNCB response, which correlated with recurrence in stages I and II disease (but not in stages III and IV). There was no correlation of any of the in vitro tests of immunofunction with recurrence in any stage. There were no correlations between any of the immune parameters and age or sex nor between DNCB reactivity and any of the in vitro responses.

Topics: Carcinoma, Squamous Cell; Concanavalin A; Dinitrochlorobenzene; Female; Head and Neck Neoplasms; Humans; Immunity, Cellular; Lectins; Leukocyte Count; Lymphocyte Activation; Male; Middle Aged; Mitogens; Neoplasm Staging; Prognosis; Recurrence; Risk; T-Lymphocytes

Blocking factors are small polypeptide molecules that may appear in the serum of patients with cancer. These factors block the transformation of lymphocytes in culture to nonspecific mitogens such as phytohemagglutinin or concanavalin A and, therefore, may reflect changes in the immunocompetence of the patient. Blocking factors were monitored during the clinical course of thirty-five patients with cancer. These factors did not develop in patients with response to therapy whereas they did develop in patients without response. A third group of patients without response to therapy after a previous remission showed an absence of lymphocyte responsiveness in culture that was not due to blocking factors, suggesting that immune clone consumption had occurred. Dermal responsiveness to tumor antigen correlated with a favorable clinical course and was usually absent when serum blocking factors were present.

Topics: Antibody Formation; Antigens, Neoplasm; Carcinoma, Squamous Cell; Concanavalin A; Humans; Immunotherapy; Lectins; Leiomyosarcoma; Lymphocyte Activation; Lymphocytes; Melanoma; Neoplasms; Osteosarcoma; Peptides; Pharyngeal Neoplasms; Rhabdomyosarcoma; Skin Tests

Human lymphocytes were stimulated in vitro with mitogens, phytohemagglutinin and concanavalin A to secrete proliferation inhibitory factor (PIF), cloning inhibitory factor (CIF), and lymphotoxin (LT). These three activities were demonstrable in the same supernatant, moreover, the particular effect observed was shown to depend on the concentration of the medium and the type of target cell employed. In general, the medium effects on target cells were: a) cytotoxic at high concentrations, b) growth inhibitory at intermediate concentrations, and c) only temporarily growth inhibitory at low concentrations. The absolute concentration producing a certain effect varied, depending on the target cell type employed. In addition, the sensitivity of the target cells to LT parallels the sensitivity of the cell to each of the other activities, PIF and CIF, and no species specificity was observed.

Topics: Adenoids; Animals; Carcinoma, Squamous Cell; Cell Division; Cell Line; Cells, Cultured; Concanavalin A; DNA; Fibroblasts; HeLa Cells; Humans; Lectins; Liver; Lymphocytes; Lymphokines; Lymphotoxin-alpha; Mice; Spleen

A comparison was made of HEp-2 cell surface changes induced by NDV or vaccinia virus infection. Three parameters were examined as a function of time after infection: the kinetics of hemadosorption and the appearance of concanavalin (con A) binding sites, and alterations in electrophoretic mobility of single cells. The kinetics of appearance of con A binding sites was strikingly similar for both virus infections, whereas hemadsorption preceded NDA synthesis and followed vaccinia synthesis. These data suggest that in the vaccinia-infected cell the hemadsorption and con A binding sites are different. NDV infection or exposure of sham-infected cells to bacterial neuraminidase significantly reduced their anodal mobilities. This also occurred after enzyme treatment of vaccinia-infected cells. Measurements of the sialic acid content of NDV or sham-infected cells before and after neuraminidase treatment indicated the exposure to the enzyme or NDV materially reduced the sialic acid content of cells. Vaccinia-infected cells contained considerably more sialic acid than did normal cells. For the vaccinia-infected cell a change in surface properties as detected by hemadsorption or increased con A binding was not reflected in a change in electrophoretic mobility.

Topics: Binding Sites; Carcinoma, Squamous Cell; Cell Line; Cell Membrane; Concanavalin A; Cytological Techniques; Electrophoresis; Hemadsorption; Kinetics; Laryngeal Neoplasms; Neuraminidase; Newcastle disease virus; Sialic Acids; Vaccinia virus; Virus Replication

Cellular immunity was assessed in patients with operable squamous cell cancer of the head and neck using in vivo skin tests and in vitro lymphocyte stimulation tests. An expansion of a previous study continued to show that 30 per cent of patients with T1N0M0 lesions were DNCB-negative and that with more advanced lesions there was further impairment. A similar finding was observed in the blastogenic response to phytohemagglutinin and concanavalin A but not pokeweed mitogen. Overall, 40 per cent of patients with resectable cancer had a significant depression of the blastogenic responses to conconavalin A and phytohemagglutinin. This depression ranged from 15 per cent in patients with T1N0M0 lesions to 71 per cent in those with T3N0M0 lesions. Although this depression was more severe in patients with palpable cervical node metastases, it was related more to the size of the primary tumor than to the nodes per se. An exception occurred in patients with large fixed nodes in whom the depression of lymphocyte stimulation was most severe. The absolute T-cell count was also depressed in patients with head and neck cancer. This depression parallelled the lymphocyte stimulation results with phytohemagglutinin and conconavalin A and was progressive with increasing stage of disease. A correlation exists between DNCB negativity and early recurrence and shortened survival. Clinical follow-up study is too short to assess the correlation of in vitro immune function with these clinical prognostic factors.

Topics: Alcoholism; B-Lymphocytes; Carcinoma, Squamous Cell; Concanavalin A; Dinitrochlorobenzene; Fluorescent Antibody Technique; Head and Neck Neoplasms; Humans; Immune Adherence Reaction; Immunity, Cellular; Immunologic Deficiency Syndromes; Leukocyte Count; Lymphatic Metastasis; Mitogens; Skin Tests; T-Lymphocytes

Topics: Agglutination; Animals; Carcinoma; Carcinoma, Squamous Cell; Cell Line; Cell Transformation, Neoplastic; Concanavalin A; Cricetinae; Fibroblasts; HeLa Cells; Humans; Kidney; Laryngeal Neoplasms; Lectins; Lung; Mice; Mouth Neoplasms; Neoplasms, Experimental; Trypsin

Topics: Agglutination; Animals; Carcinoma; Carcinoma, Squamous Cell; Cell Line; Cell Membrane; Cell Transformation, Neoplastic; Chick Embryo; Concanavalin A; Cricetinae; Cycloheximide; Cytarabine; Floxuridine; Humans; Immune Sera; Kidney; Laryngeal Neoplasms; Lectins; Methods; Newcastle disease virus; Simplexvirus; Time Factors; Trypsin; Vitamin A