Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human peripheral blood or lymph node lymphocytes, obtained from patients with a variety of lung cancer, were incubated in vitro with mitomycin C-treated tumor monolayers in the presence of T-cell growth factor. The cytotoxicity of these lymphocytes for autologous tumor cells (autologous killer activity) was assessed by a 4-hr 51Cr-release assay. Cytotoxic activity was observed in 14 out of a total of 20 cases. Lymphocytes from patients with squamous cell carcinoma, large cell carcinoma and carcinoid exhibited positive activity levels of 11.1 +/- 1.8, 16.3 and 23.9% respectively. Nine out of 13 patients with adenocarcinoma exhibited positive activity with a mean value of 8.8 +/- 6.8%. No lymphocyte activity against small cell carcinoma was observed. Natural killer (NK) activity did not always correlate with autologous killer (AK) activity. Treatment of lymphocytes with monoclonal anti-human lymphocyte antibody revealed differences in effector cell populations concerning these two activities; AK activity was abrogated only by treatment with anti-human Lyt 3 antibody and complement, whereas NK activity was abrogated by anti-human Lyt 1, 2 and 3 and partially by anti-human Ia antibody. These results indicate that AK activity is mediated exclusively by T cells, but that NK activity is mediated by several subpopulations of lymphocytes such as T cells, null cells and others.
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PMID:Cytotoxicity tests against cultured human lung cancer cells with autologous lymphocytes activated in vitro by mitomycin C-treated tumor monolayers in the presence of T-cell growth factor. 630 Apr 83

In human long-term marrow cultures granulomonopoiesis is maintained for several weeks. Studies on granulomonocytic progenitors (CFU-GM) and their progeny have shown that survival, proliferation, differentiation and maturation of these cells are controlled by a set of glycoproteins, the colony-stimulating factors (CSFs) and the Steel factor. We have studied the expression of these factors using reverse transcriptase polymerase chain reaction (RT-PCR) in 17 adherent layers of normal bone marrow at 3, 5 or 7 weeks of culture. We have taken the 5637 bladder carcinoma cell line as a control for expression of GM-CSF, M-CSF, G-CSF and Steel factor, and PHA-activated T lymphocytes as a control for expression of multi-CSF (interleukin 3, IL-3). We have found that GM-CSF was expressed in the 17 adherent layers without induction by interleukin 1 beta (IL-1 beta). M-CSF was also detected in all cases, but in two early-stage (week 3 and week 5) cultures only after stimulation by IL-1 beta. G-CSF was detected in only 11 cases (three without IL-1 beta, and eight after addition of IL-1 beta). Steel factor was detected in 14 cases (ten without IL-1 beta, and four after addition of IL-1 beta). IL-3 was not detected even by means of nested RT-PCR. These data indicate in six late-stage (week 5 or week 7) cultures G-CSF messenger concentrations 10(3)-fold less than in 5637 control cells (for an identical amount of total cellular RNA). A similar conclusion may be drawn for Steel factor in three late-stage cultures. For IL-3 our negative results indicate a messenger concentration 10(5)-fold less than in activated T lymphocytes. These results suggest a crucial role for GM-CSF and M-CSF in the maintenance of granulomonopoiesis in human long-term cultures. The role of G-CSF and Steel factor may be more marginal. Eventually IL-2 may not be involved in the regulatory process.
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PMID:The detection of colony-stimulating factors and steel factor in adherent layers of human long-term marrow cultures using reverse-transcriptase polymerase chain reaction. 751 Mar 57

We have investigated the role of cytokines (IL-2, IL-3, IL-4, IL-6, IFN-gamma, and GM-CSF) in the generation of primary cytotoxic T lymphocytes (CTL), within a single tumor system. The murine carcinoma line 1 was transfected with expression vectors with cDNA for these cytokines. Line 1 expresses low levels of class I MHC molecules, but can be induced with dimethyl sulfoxide or IFN-gamma to express high levels of class I. Class I low line 1 cells are not susceptible to CTL lysis, while class I high line 1 are lysed by CTL, which allows us to assay for CTL activity. To isolate primary CTL, tumor-infiltrating lymphocytes were isolated from cytokine-expressing or control tumors, growing in vivo. Most cytokines stimulated nonspecific killers, but IL-2 and IL-3 stimulated primary CTL. While IFN-gamma alone did not generate primary CTL, coexpression of IFN-gamma with IL-2 resulted in CTL generation. This is the first comparison of the effects of a series of cytokines on primary CTL development, and has important implications for vaccine development and immunotherapy.
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PMID:Analysis of the effect of cytokines (interleukins 2, 3, 4, and 6, granulocyte-monocyte colony-stimulating factor, and interferon-gamma) on generation of primary cytotoxic T lymphocytes against a weakly immunogenic tumor. 755 82

Human carcinomas spontaneously express abundant IL-2R beta but little IL-2R alpha on the cell surface, contain mRNA for IL-2R beta- and IL-2R alpha-chains, and may be inhibited in growth by exogenous IL-2. To study the relationship between IL-2R expression and growth inhibition by IL-2, carcinoma cells were transduced with IL-2R alpha and IL-2R gamma cDNAs or IL-2R beta antisense cDNA. Transfectants with the IL-2R alpha gene expressed high levels of the alpha- and beta-receptor chains and showed increased binding of [125I]IL-2. Exogenous IL-2 at the picometer concentrations inhibited their growth, and Abs to IL-2R alpha- or IL-2R beta-chains reversed the inhibition. After transduction of IL-2R beta antisense cDNA, gastric carcinoma (HR) cells no longer expressed IL-2R beta-chain, and their proliferation was depressed in the absence of exogenous IL-2. Transduction of IL-2R gamma-chain cDNA into tumor cells increased sensitivity to growth inhibition by exogenous IL-2 of a squamous cell carcinoma line, but not of HR or renal cell carcinoma lines. All of the parental and transduced tumor cell lines were found to constitutively express intracellular IL-2, detectable by immunostaining or flow cytometry of permeabilized cells. IL-2 was present on the surface of some tumor cells. Intracellular IL-2R beta and IL-2R gamma proteins were also detectable in tumor cells. Using reverse-transcription PCR combined with Southern blots or in situ hybridization, mRNA for IL-2 was found to be present in parental and transduced tumor cells. Expression on human carcinomas of IL-2R beta, inhibition of their growth by IL-2R beta antisense cDNA, and their ability to constitutively produce IL-2 and its presence on the cell surface, all suggest that endogenous IL-2 may play a role in tumor cell growth.
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PMID:Constitutive production of IL-2 by human carcinoma cells, expression of IL-2 receptor, and tumor cell growth. 759 83

Peripheral blood T lymphocytes from 15 patients with gastric carcinoma and 6 normal healthy controls were evaluated for Interleukin-2 R gene expression. Total RNA was extracted from T cell-enriched fractions of patients as well as from control peripheral blood lymphocytes, with or without mitogenic stimulation. The presence of mRNA for IL-2 R alpha evaluated by Northern blot analysis revealed that unstimulated T cells expressed lower levels of IL-2 R mRNA than PHA stimulated T cells. Expression of both IL-2 R alpha transcripts (3.5 and 1.5 Kb) were either not detectable or only weakly detectable on T lymphocytes from patients even after mitogenic stimulation. In contrast, a significant rise in the expression of both IL-2 R alpha transcripts was observed on T cells from normal controls followed by mitogenic challenge. This paper reports on the defective IL-2 R alpha gene expression in gastric carcinoma patients, which may explain one of the causes of immunodeficiency associated with neoplastic transformation and progression.
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PMID:Defective interleukin-2 R gene expression in gastric carcinoma patients. 762 94

A previously identified humanized anti-CD3 Ab variant, v9, binds T cells with > 100-fold higher efficiency than the original variant, v1, and almost as efficiently as a chimeric molecule containing corresponding murine variable domains. Variants v1 and v9 differ at six positions in the H chain second CDR. Here a mutational analysis was used to identify which of these six replacements are primarily responsible for the difference in binding efficiency. These anti-CD3 variants were used to probe the relationship between Ag binding efficiency and potency in stimulating T cell proliferation. The human to mouse mutations T57S and V63F increase the binding efficiency of variant v1 for T cells by 8- and 12-fold, respectively, and together in variant M18 enhance binding by 26-fold to within 4-fold of variant v9. A framework mutation, 169L, was identified that enhances the binding of variants v1 and M18 by 14- and 3-fold, respectively. The Ag binding efficiencies of anti-CD3 variants correlate directly with their potencies in stimulating the proliferative activity of both resting human PBMC and IL-2-activated human T lymphocytes. Humanized variant v9 is equipotent to the murine parent Ab in stimulating ATL activity. PBMC activated by variants v1 and v9 IgG in a short term culture are equally cytotoxic against human breast carcinoma cells. Thus, high efficiency Ag binding by anti-CD3 variants is important for stimulating efficient T cell proliferation, but not cytotoxicity, in vitro.
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PMID:Identification of heavy chain residues in a humanized anti-CD3 antibody important for efficient antigen binding and T cell activation. 763 41

Serum IL-2 and sIL-2R levels were measured with sandwith ELISA assay before and after surgery or transarterial embolization in 19 cases of primary hepatic carcinoma. The results show that pretreatment IL-2 levels of patients were significantly lower and sIL-2R expression was higher than those of normal control. IL-2 levels of patient were increased and sIL-2R expression was decreased after treatment. The results suggest that the changes of IL-2 level and sIL-2R expression may be closely related to treatment, recurrence and prognosis of patients with primary hepatic carcinoma.
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PMID:[Changes in serum IL-2 and sIL-2R levels in patients with primary hepatic carcinoma before and after treatment and their clinical significance]. 765 84

We report the immunomodulatory effects of an intravenous treatment with F(ab')2 fragments of the bispecific monoclonal antibody BIS-1 during subcutaneous recombinant interleukin 2 (rIL-2) therapy of renal cell cancer (RCC) patients. BIS-1 is directed against both the CD3 antigen on T cells and the EGP-2 molecule on carcinoma cells and some normal epithelia. The amount of BIS-1 F(ab')2 bound to peripheral blood lymphocytes (PBLs) increased dose-dependently. This occupation degree was highest at the end of the 2 h infusion and rapidly decreased subsequently. During the first hour of BIS-1 F(ab')2 infusion the number of PBLs decreased slowly. This was followed by an increase in serum tumour necrosis factor alpha (TNF-alpha) concentrations and a rapid decrease in the numbers of peripheral blood lymphocytes, monocytes and eosinophils. In our view, the most likely explanation for the observed decrease in occupation degree of BIS-1 F(ab')2 and the rise in TNF-alpha levels is based on the assumption that BIS-1-carrying T cells leave the circulation. The CD3 antigens on these extravasated T cells become cross-linked by EGP-2 antigens, inducing TNF-alpha secretion. This results in an enhanced decrease in the numbers of PBLs, monocytes and eosinophils. These preliminary results suggest that BIS-1 F(ab')2 treatment during IL-2 therapy may induce local T-cell activation.
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PMID:Immunomodulatory effects of intravenous BIS-1 F(ab')2 administration in renal cell cancer patients. 766 98

A neoplastic human salivary intercalated duct cell line, HSG and its derivative HSG-AZA1 cells with a myoepithelial cell phenotype and HSG-AZA3 cells with an acinar cell phenotype, which were induced by treatment of HSG cells with 5-azacytidine, have been used in our laboratory as models for studying mechanisms regulating cytodifferentiation in salivary glands as well as for developing differentiation therapy for salivary gland tumors. Consequently, it has been shown that the treatment of HSG, HSG-AZA1 and HSG-AZA3 cells with various differentiation agents results in cellular differentiation into myoepithelial, acinar or neuronal cells as well as keratinizing squamous cells, chondrocytes, and osteoblast, with a concomitant decrease of anchorage-independent and anchorage-dependent growths in addition to decreased tumorigenicity in nude mice. It was also found that the treatment of an adenoid cystic carcinoma of the maxillary sinus with adoptive immunotherapy involving intra-arterial injection of LAK cells and IL-2 in combination with radiotherapy, resulted in bone formation in the treated tumor, which was then replaced completely by lamellar bone tissue with myxomatous stroma. These findings may suggest the potential usefulness of differentiation therapy in human salivary gland tumors.
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PMID:[Differentiation therapy for salivary gland tumors]. 768 83

The influence of galactoside-specific mistletoe lectin (ML-1) administration on defined acute phase reactants in the serum of cancer patients (mammary carcinoma, n = 4; larynx carcinoma, n = 11; TNM-stages II to IV; after appropriate surgery, chemotherapy, radiation) was studied. Regular subcutaneous injections of the optimal doses of ML-1 (1 mg/kg body weight, twice a week) yielded statistically significant increases of certain acute phase reactants (C-reactive protein, haptoglobin, coeruloplasmin, C3-complement, albumin, immunoglobulin IgM) after four weeks of treatment. However, serum concentrations of transferrin, C4-complement and the immunoglobulins IgG and IgA were found within the biological range (means +/- 2 s). The increase of acute phase reactants after administration of ML-1 correlates positively with the activity of lymphatic cells (e.g. expression of IL-2 and HLA-DR receptors) in FACS (fluorescence-activated cell sorter) staining experiments and indicates the immunoreactive potency of this substance which may be speculated to be cytokine-induced.
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PMID:[Effect of mistletoe lectin therapy on serum level of defined serum proteins (acute phase proteins) in tumor patients]. 768 1


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