Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly purified human recombinant interleukin 2 induced cytotoxicity in mouse spleen cells against mouse sarcoma cells when added during the 51Cr microcytotoxicity assay. It elicited similar levels of killer cell activation as did human lymphoid (Jurkat leukaemia-derived) or mouse lymphoid (EL-4 leukaemia-derived) IL-2 preparations. The susceptibility of six MC-induced mouse sarcomas to the cytolytic effect of lymphokine-activated killer cells was compared. Five (MC11, MC13, MC14, MC15, MC16) of six mouse sarcoma cell lines examined were sensitive in vitro to the LAK cell effect, whereas one cell line (MC12) was resistant. Since the sensitive and resistant target cell lines had been induced with the same carcinogen and in mice of the same genotype, they represent a very useful model for investigation of target cell structures responsible for the sensitivity to the LAK cell effect.
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PMID:Immunotherapy of murine sarcomas with interleukin 2. II. Activation of killer cells by human recombinant IL-2. 349 97

Peripheral blood lymphocytes obtained from patients by leukapheresis were cultured in RPMI 1640 containing human plasma and interleukin 2. The morphology, phenotypes and cytotoxicity of induced LAK cells were studied. Lymphoblastoid cells mainly proliferated were OKIa1+ cells and were thought to be LAK cells. Maximal cytotoxicity was obtained after two weeks of incubation. IL-2 enhanced the cytotoxicity of LAK cells. Autologous LAK cells induced by two weeks of incubation were injected into patients. One case of pulmonary metastases of breast cancer showed reduction and two lesions showed partial regression. Also, no new lesions appeared in the lungs of a patient with alveolar soft-part sarcoma.
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PMID:[Adoptive immunotherapy of malignant diseases with LAK cells]. 349 32

Experiments were designed to test what percentage of experimental MC-induced murine sarcomas were sensitive to the local tumour inhibitory effect of IL-2 and whether any correlation existed between the sensitivity of these sarcomas to the immunotherapeutic effect of IL-2 and their susceptibility to the cytolytic effect of IL-2-activated killer cells. It was found that the sensitivity of MC-induced sarcomas to local IL-2 immunotherapy was a general phenomenon. Repeated peri-tumoural injections of RIL-2 inhibited the growth of five (MC11, MC13, MC14, MC15, MC16) out of six sarcomas in syngeneic mice. The sixth murine sarcoma (MC12) was found to be resistant to the tumour inhibitory effect of IL-2. Similarly, five (MC11, MC13, MC14, MC15, MC16) out of six murine sarcoma cell lines were sensitive to the cytolytic effect of IL-2-activated syngeneic killer spleen cells when examined in vitro, whereas the sixth (MC12) sarcoma cell line was resistant. These results suggest that LAK cells represent the effector cell mechanism responsible for the anti-tumour efficacy of local IL-2 immunotherapy and that in vitro testing of sensitivity to the LAK cell-mediated cytolysis may be used to detect tumours responding to IL-2 immunotherapy in vivo.
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PMID:The anti-tumour efficacy of human recombinant interleukin 2. Correlation between sensitivity of tumours to the cytolytic effect of LAK cells in vitro and their susceptibility to interleukin 2 immunotherapy in vivo. 349 54

IL-2-activated killer cells (LAK cells) are potent effectors of adoptive immunotherapy in advanced cancer patients. We have undertaken fundamental experiments and a clinical pilot study in order to search for an efficient way of applying this therapy. Characterization of LAK cells: Human peripheral blood lymphocytes were fractionated by Ficoll-Isopaque and Percoll gradient centrifugation. The main activity was located in the low-density fraction (less than 1.061 g/ml), which corresponded to the LGL/NK fraction. However, the behavior of LAK cells against metabolic inhibitors such as DMSO, NDGA, EtOH and NaN3 was quite different from that of NK cells. LAK cells are resistant to lipoxygenation inhibitors and are labile to mitochondrial oxidation inhibitor, opposite to the behavior of NK. All the fractions sorted by FACS using CD16 and CD3 expressed LAK activity. This phenomenon was missed because LAK cells are sensitive to NaN3 which is usually contained in buffers of MoAb and in the running solution of cell sorter. Simulation study: The side effects and efficacy of LAK transfer were evaluated using Meth A sarcoma cell-bearing BALB/c mice. No side effects were observed and significant efficacy was obtained in mice whose tumors were located in the lung or abdominal cavity. Human pilot study: The pilot study was conducted in 25 patients with advanced carcinomas. Therapeutic efficacy was obtained in patients for whom local transfer was undertaken rather than systemic administration.
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PMID:[Transfer of interleukin 2-activated lymphocytes]. 349 56

Interleukin 4 (IL-4) expresses multiple biologic activities, including B cell, mast cell, and T cell stimulation. We showed that the incubation of resting splenocytes from C57BL/6 mice solely in purified native or recombinant mouse IL-4 results in the generation of lymphokine-activated killer (LAK) activity directed against fresh, syngeneic sarcoma cells. The precursor activated by IL-4 expresses surface asialo-GM1. In addition, IL-4 is capable of amplifying the splenic LAK activity induced by recombinant IL-2. The generation, by IL-4, of killer cells with broad antitumor reactivity raises the possibility of using IL-4 alone or in combination with IL-2 in the immunotherapy of cancer in animal models.
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PMID:Interleukin 4 (B cell stimulatory factor 1) can mediate the induction of lymphokine-activated killer cell activity directed against fresh tumor cells. 349 2

Supernatants from ConA-stimulated rat spleen cell cultures and from cultures of PMA-stimulated murine lymphoma subline EL-4TF were found to contain TCGF and to inhibit growth of a transplantable, MC-induced sarcoma MC11 in syngeneic mice. Tumour-inhibitory effects of the supernatants were dependent on local and repeated administration. Prior to use of the supernatants obtained from PMA-stimulated EL-4TF cell cultures, the dialysable PMA had to be removed; contamination with PMA was found to abolish the tumour-inhibitory effect of the supernatants and to produce enhancement of tumour growth. A significant tumour-inhibitory effect has also been obtained with partially purified TCGF prepared from culture supernatants of cloned EL-4TF cells by ammonium sulphate precipitation, ion-exchange (FPLC) chromatography, and AcA 44 Ultrogel filtration.
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PMID:Tumour inhibitory effects of TCGF/IL-2/-containing preparations. 387 65

In the present article we describe studies on a chemically induced sarcoma in DA rats. This tumor expresses a unique antigen which can be demonstrated by both syngeneic antibodies and cytotoxic T cells. We have established cytotoxic T-cell lines (CTLs) specific for the tumor and with high efficient killing capacity in vitro. When testing for the ability of such CTLs to inhibit tumor out-growth in vivo, we found that they had to be inoculated together with the tumor and in the presence of T-cell growth factor to provide any significant degree of protection. We thus believe not only that there is a requirement for addition of CTL-stimulating lymphokines in vivo, but also that the CTLs fail to move from one site in vivo to attack relevant tumor cells at another site. No evidence was obtained that the CTLs gradually could acquire such migratory ability in vivo.
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PMID:Studies on chemically induced rat tumors. II. Partial protection against syngeneic lethal tumors by cloned syngeneic cytotoxic T lymphocytes. 641 34

Immunoregulatory factor (IRF) is a 70,000 molecular weight glycoprotein produced by human tumors that suppresses lymphocyte function including mitogen-stimulated tritiated leucine (3H-leu) and tritiated thymidine (3H-Tdr) uptake, in vitro immunoglobulin synthesis, induction of allospecific cell-mediated cytotoxicity, and proliferation of T-cell growth factor-dependent lymphocyte cultures. Antisera to IRF were produced by immunization of goats and rabbits with IRF purified by diethylaminoethyl (DEAE)-anion exchange and affinity chromatography. Antisera specificity was demonstrated by binding to IRF but not control muscle extract in an ELISA test and by specific removal of IRF activity by antibody coupled to acrylamide beads. Using these antisera, a double antibody-binding assay was developed to measure circulating levels of IRF and to determine its relationship to tumor growth and relevance for monitoring the clinical course of cancer patients. Quantitative autologous as well as allogeneic binding of sarcoma patients' sera to anti-IRF antibody was demonstrated. Of five tumor extracts tested, two had immunosuppressive activity, and IRF was detected in the preoperative sera of both patients. These extracts were not suppressive and IRF was not detected in the preoperative sera of these patients. In a double-blind study, analysis of serial serum samples from 26 sarcoma patients, 11 normal volunteers, and eight noncancer patients, demonstrated four patterns of circulating IRF: sustained high levels, increasing levels, decreasing levels, and no detectable IRF. Seven of 14 patients who eventually developed metastatic disease demonstrated sustained high or increasing levels of IRF. Eleven of 12 patients clinically free of tumor for five years or more, ten of 11 normal volunteers, and eight of eight noncancer patients had either a pattern of decreasing levels or no detectable IRF. Circulating IRF levels are correlated with the presence of tumor and may be useful in monitoring the clinical course of cancer patients.
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PMID:Detection of a suppressive immunoregulatory factor (IRF) in the sera of sarcoma patients by enzyme-linked immunoassay (ELISA) and correlation with clinical course. 687 4

We have investigated the use of T-cell growth factor (TCGF) to isolate and grow, in long-term culture, lymphoid cells with immunologic reactivity directed against syngeneic murine and autologous human tumors. Splenocytes from mice immune to a methylcholanthrene-induced sarcoma were expanded in TCGF, both before and after in vitro mixed lymphocyte-tumor cultures, and expressed high levels of cytotoxicity for fresh syngeneic solid tumor cells. Cloned lines have been isolated with a high level of specific lysis for the immunizing tumor. Similar studies of cytotoxic reactivity to a syngeneic FBL-3 lymphoma have given rise to long-term cytotoxic cell lines growing in TCGF capable of curing mice with disseminated lymphoma in adoptive transfer studies. Exposure to TCGF, of human peripheral lymphoid cells from cancer-bearing patients, results in the development of cytotoxicity to autologous fresh tumor. We have used clonal analysis by limiting dilution techniques to isolate individual cloned cells with this autologous antitumor reactivity. Infusion to autologous cytotoxic cells expanded 10,000-fold in TCGF and labeled with 111In into three cancer patients resulted in cell localization initially to the lung and subsequently to the liver and spleen. The application of these techniques for the cloning and expansion of antitumor T-lymphoid cells in TCGF has offered a new approach to adoptive immunotherapy.
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PMID:Development of long-term cell lines and lymphoid clones reactive against murine and human tumors: a new approach to the adoptive immunotherapy of cancer. 698 Apr 92

FK506 and cyclosporin A (CsA) are immunosuppressive agents that inhibit IL-2 production by activated T cells, but only CsA inhibits IgE activation-induced cytokine transcripts in mouse IL-3-dependent, bone marrow-derived mast cells (BMMC). We previously associated the resistance of BMMC to FK506 with a deficiency in the expression of FK506 binding protein (FKBP) 12, a molecule that forms a complex with FK506 capable of inhibiting calcineurin phosphatase activity in vitro. In this report, we establish that FKBP12 mediates FK506 inhibition of both calcineurin phosphatase activity and IgE activation-induced cytokine transcripts in a Kirsten murine sarcoma virus-immortalized mast cell line that is FKBP12 deficient. Overexpression of FKBP12 by transfection enhanced the ability of FK506 to inhibit calcineurin phosphatase activity (IC50 = 2 nM), compared with cells transfected with the expression vector alone (IC50 > 30 nM). The IC50 value for FK506 inhibition of IgE activation-induced transcripts for TNF-alpha decreased from 40 nM in vector control cells to 10 nM in FKBP12 transfectants. Similarly, the IC50 value for inhibition of IL-6 transcripts decreased from > 1000 nM in vector control cells to 35 nM in FKBP12 transfectants. In contrast, activation-elicited release of the secretory granule mediator beta-hexosaminidase was only partially inhibited by FK506 at 1000 nM, regardless of the levels of FKBP12 expressed by the cells. Thus, FKBP12 is the dominant cytosolic protein that mediates FK506 inhibition of TNF-alpha and IL-6 transcripts.
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PMID:The complex of FK506-binding protein 12 and FK506 inhibits calcineurin phosphatase activity and IgE activation-induced cytokine transcripts, but not exocytosis, in mouse mast cells. 753 Jul 43


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