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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NK cells can recognize and destroy a broad range of cells, including many tumor cells and virally infected cells, yet spare most normal cells. Identification of the target structure recognized by these cells has proved elusive. An attractive hypothesis is that, unlike B cells and T cells that recognize a specific foreign marker, NK cells respond to the absence of a "self" marker. Class I MHC molecules have been implicated as the self markers whose absence can trigger lysis. We show here that normal cells are lysed on incubation with IL-2-activated NK cells if peptides that can bind to the class I MHC molecules of the normal cells are also included in the assay, and speculate that this binding is somehow removing a self marker that normally protects a cell from lysis. NK cells were derived from splenocytes of young (5 to 8 wk old) athymic nude BALB/c (H-2d) or nude C57Bl/6 (H-2b) mice incubated with 1000 U/ml rIL-2, and target cells were derived from splenocytes of normal BALB/c or C57Bl/6 mice incubated with Con A. Peptides were from xenogeneic, viral, self, and mutated self protein sequences and included sequences specific for Kd, Kb, Db, and Ld. All peptides increased lysability of those targets to which they could bind.
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PMID:Effect of class I MHC binding peptides on recognition by natural killer cells. 143 Oct 94

During inflammation and recirculation, lymphocytes migrate into tissues by traversing the capillary endothelium, a process known as extravasation. After crossing the endothelial cells, lymphocytes come into contact with the basement membrane, which is a specialized layer of extracellular matrix containing predominantly laminin, collagen type IV, entactin, and heparan sulfate proteoglycans. In tissue invasion by inflammatory cells and metastatic tumor cells, the basement membrane serves as a substratum for cell adhesion and migration. However, the role of basement membrane in lymphocyte extravasation remains unclear. In this study, we investigated the effect of basement membrane on lymphocyte adhesion, migration, and proliferation, using matrigel as a model for basement membrane. We observed that matrigel promotes both lymphocyte adhesion and migration, with entactin primarily responsible for promoting adhesion and laminin for promoting migration. In addition, activation of lymphocytes by anti-CD3 enhances their adhesion and migration on matrigel-coated substratum. We also observed that matrigel inhibits the proliferation of lymphocytes stimulated by Con A. Furthermore, we demonstrated that laminin is the matrigel component responsible for inhibiting lymphocyte proliferation. However, matrigel has no effect on the proliferation of lymphocytes stimulated by LPS. These results suggest that matrigel has different effects on lymphocyte subpopulations. In agreement with the results on proliferation, matrigel also inhibits the production of IL-2 by Con A-stimulated lymphocytes.
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PMID:Basement membrane and its components on lymphocyte adhesion, migration, and proliferation. 143 Oct 96

Enzyme characteristics of in vitro activated peritoneal macrophages of normal and BP6-TU2 tumor-bearing rats were compared with those of nonactivated macrophages. The activating effect of LPS, IFN-gamma, IL-2, TPA, TNF and Zymosan was assessed by the determination of the activities of alpha-naphthyl butyrate esterase (ANBE), tartrate-resistant acid phosphatase (TRAP), beta glucuronidase (BG) and 5'nucleotidase (5'NT). The used individual activators induced the macrophage enzyme activities in different degrees. LPS, TPA and TNF appeared to be the most effective activators of enzyme activities in macrophages of normal rats. IFN-gamma, IL-2 and Zymosan were less effective. The macrophages of BP6-TU2 tumor-bearing rats were less sensitive to the stimulatory effect of activators with respect to their enzyme activation capacity, except for TRAP activity. The results indicate that enzyme ANBE is an adequate marker of rat peritoneal macrophages. Enzyme TRAP determines the macrophage activation degree more expressively, in comparison with BG and 5'NT. The differences in enzyme activities could be a suitable marker of macrophage activation and might suggest the dependence on the pathway of macrophage stimulation by distinct activators.
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PMID:Cytochemical study of activated peritoneal macrophages in normal and tumor-bearing rats. 143 43

T-cell-rich B-cell lymphomas (TCRBCLs) are diffuse lymphomas that contain a minority of large neoplastic B cells amidst a majority of non-neoplastic T cells and numerous histiocytes, an unusually pronounced reactive component not seen in most diffuse large B-cell lymphomas (DLBCLs). This reaction may be influenced by various cytokines secreted by lymphoma or reactive cells; therefore, expression of interleukin (IL)-1 beta, IL-2, IL-4, IL-6, and IL-9 was evaluated immunohistochemically on paraffin-embedded sections of 18 TCRBCLs and was compared with that of 15 DLBCLs containing a minority of reactive T cells and to that of seven reactive lymph nodes. Moderate to intense expression of IL-4 was detected in variable numbers of tumor cells and in numerous histiocytes in 16 TCRBCLs. In contrast, intense IL-4 expression in numerous histiocytes was observed in only one of 15 DLBCLs with few T cells. In four other DLBCLs and three reactive nodes, moderate to intense staining for IL-4 was noted only in rare large transformed cells or in occasional histiocytes. Except for one IL-1 beta positive and another IL-9 positive TCRBCL, there was no marking or weak staining only with other cytokine antibodies in the neoplastic and reactive cases studied. The expression of IL-4 in most TCRBCLs, but not in other DLBCLs or in reactive nodes, suggests that this cytokine is one factor involved in the pathobiology of the abundant T-cell reaction and, perhaps, contributes to the paucity of neoplastic B cells in TCRBCLs.
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PMID:Interleukin-4 may contribute to the abundant T-cell reaction and paucity of neoplastic B cells in T-cell-rich B-cell lymphomas. 144 42

Interleukin-2 receptors are composed of at least two polypeptide chains of alpha (55KD) and beta (75KD). The IL-2R beta chain is an essential component of the functional receptor for signal transduction of IL-2. We previously reported the distribution of IL-2R subunits among peripheral blood mononuclear cells. We here present some data regarding the expression of IL-2R subunits on various hemopoietic malignant cells. Fresh leukemic cells obtained from adult T cell leukemia patients expressed both alpha and beta chains, and leukemic cells derived from some patients with T cell leukemia, B cell leukemia or myeloid leukemia expressed the alpha and/or beta chain of IL-2R. The IL-2R beta chain on these leukemic cells were demonstrated to be functional for cell growth signaling. IL-2R alpha and beta chains should be tumor markers.
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PMID:[The expression of IL-2 receptor subunits on various leukemic cells]. 144 19

We examined the effect of fibrin coagulation on tumor cytotoxicity mediated by human lymphokine (IL-2)-activated killer (LAK) cells. LAK cells were induced from peripheral blood mononuclear cells (MNC) by culture with recombinant IL-2 for 4 or 5 days, and LAK cell-mediated cytotoxicity against tumor cells was assessed by 51Cr release assay in the presence or absence of plasma from normal subjects and lung cancer patients. Plasma did not affect the phase of induction of LAK activity by IL-2, but dose-dependently inhibited the effector phase of LAK cell-mediated cytotoxicity against Daudi cells. Similar inhibition of LAK cell-mediated cytotoxicity was observed on pretreatment of Daudi cells and human lung cancer cell lines with human fibrinogen plus thrombin. A parallel relationship was found between the amount of fibrinogen in plasma of lung cancer patients and inhibition of LAK cytotoxicity. This inhibition was reduced by addition of anticoagulants (heparin or argatroban). These findings suggest that fibrin coagulation on tumor cells protects them from LAK cell-mediated tumor cytotoxicity in malignant lesions and that a combination of an anticoagulant drug and IL-2/LAK therapy may be effective for treatment of lung cancer patients.
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PMID:Inhibition by fibrin coagulation of lung cancer cell destruction by human interleukin-2-activated killer cells. 145 61

Ukrain is a semisynthetic compound consisting of alkaloids from Chelidonium majus L. conjugated to thiophosphoric acid, with immunomodulatory and therapeutic properties in cancer patients. The present in vitro studies demonstrate that Ukrain is an effective biological response modifier in that it augmented, by up to 48-fold, the lytic activity of spleen lymphocytes obtained from alloimmunized mice. The lytic activities of IL-2-treated spleen cells and peritoneal exudate lymphocytes were also increased significantly by the addition of Ukrain to the CML assay medium. The highest Ukrain-induced enhancement of spleen lymphocyte lytic activity in vitro was found to occur at 18 days after alloimmunization, was dose dependent and specific for the immunizing P815 tumor cells. Since Ukrain was present only during the CML assays, its mode of action is thought to be via direct activation of the effector cell's lytic mechanism(s).
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PMID:Activation of spleen cell lytic activity by the alkaloid thiophosphoric acid derivative: Ukrain. 146 76

The effects of glioma culture supernatant (GCS) and interleukin-2(IL-2) on the motility of autologous stimulated lymphocytes (ASL) were studied by using collagen gel system, chemotaxic chamber system and flow cytometric analysis. GCS inhibited the migration of ASL into collagen gel. It enhanced the ASL motility and the expression of CD 26 antigen on the cell surface. IL-2 inhibited the migration of ASL into collagen gel and had no influence on the motility of ASL, but enhanced the expression of CD 26 antigen. On the other hand, a clinical glioma specimen showed limited depth of ASL migration when injected into the tumor cavity in addition to the formation of fibrin like membrane on its surface and a layer of degenerated ASL under it. To make ASL therapy more effective to malignant glioma, the following measures should be recommended; 1) inject adequate volume of IL-2 into tumor cavity, 2) reduce the frequency of ASL administration, 3) wash out of glioma secreting factors, degenerated ASL and glioma cells in addition to reduce the volume of tumor tissue.
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PMID:[The motility of IL-2 activated lymphocytes into malignant glioma]. 147 10

Peripheral blood lymphocytes obtained from 2 patients with hypopharyngeal cancer were cultured with mitomycin C treated autologous tumor cells (autologous MLTC) for 10 days and further cultured with recombinant interleukin 2 (rIL-2). In one case 10-day MLTC induced increase of CD25-positive lymphocyte count, indicating that IL-2 receptors were expressed dominantly by the autologous tumor stimulation, and further culture with rIL-2 differentiated killing activity against autologous tumor cells. In the other case, however, MLTC alone induced killing activity against autologous tumor cells, indicating that the tumor cells from this patient might possess stimulatory activity sufficient to induce mature killer cells. Electron microscopic observation of the morphological features of lymphocytes cultured for 10 days revealed mostly small lymphocytes with low incidence of cytoplasmic granules. Further culture with rIL-2, however, induced slightly larger lymphocytes with well-developed microvilli, and cytoplasmic granules were found in many of the cells. Lymphokine activated killer (LAK) cells induced by culture of lymphocytes with rIL-2 alone were much larger and had long microvilli and abundant cytoplasmic granules, and were apparently morphologically different from the killer cells initiated by MLTC. The small lymphocytes induced by autologous MLTC alone might be autologous tumor specific cytotoxic T lymphocytes (CTL) and/or CTL precursors. Further culture with rIL-2 induced maturation of the CTL. However, the nature of the cytoplasmic granules remains obscure.
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PMID:Electron microscopic observation of killer cells induced by mixed culture of lymphocytes with autologous cancer cells and further culture with recombinant interleukin-2. 148 83

We have studied the effects of interleukin-4 (IL-4) on the expansion, proliferation, phenotype, and antitumor activity of tumor-infiltrating lymphocytes (TIL) derived from human renal cell carcinoma. Cultures were obtained from three primary renal tumors and one group of tumor-invaded, regional lymph nodes. IL-4 induced a significant increase in lymphocyte expansion and proliferation, but the response was dependent on the concurrent dose of IL-2 in culture. Increased growth activity was only observed in those cultures receiving low doses (20 U/ml) of IL-2 (average increase of fold expansion of 6.5, P < 0.01) with no changes in growth activity in the high dose (1000 U/ml) cultures. The combination of low dose IL-2 and IL-4 (200 U/ml) promoted lymphocyte growth significantly better than high dose IL-2 alone, the current standard growth regimen for in vitro expansion of TIL. TIL grown in the presence of IL-4 significantly reduced the level of non-specific, non-major histocompatibility complex-restricted antitumor activity (P < 0.01 for allogeneic renal, nonrenal, and NK-sensitive K562 cells), while exhibiting no effect on the level of autologous killing. This is in contrast to previous findings of significant enhancement of autologous antitumor activity using IL-4 on tumor-specific, melanoma-derived TIL. We also evaluated the effects of irradiated autologous tumor stimulation (TIL:tumor ratio, 10:1) on TIL cultures. Addition of autologous tumor cells increased expansion and proliferation of all cultures regardless of concurrent lymphokines present in the culture media (average increase fold expansion of 2.21, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulatory effects of interleukin-4 on tumor-infiltrating lymphocytes derived from human renal cell carcinoma. 149 94


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