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

The expression of Fas antigen at the surface of renal cell carcinoma and the susceptibility to Fas-mediated lysis by a tumor specific CTL clone were investigated. Renal cell carcinoma cell lines expressed Fas antigen and were susceptible to apoptosis mediated by antibodies to Fas/APO1. Using RT-PCR, we further showed that these cell lines expressed mRNA for Fas deleted transmembrane region, corresponding to a soluble form of Fas/APO-1. To investigate the role of the Fas/FasL pathway in the cytotoxic response against RCC cells, we analyzed the induction of Fas-L on a tumor specific T cell clone (CTL8C2), previously generated against one RCC cell line. Fas-L expression on CTL8C2 was detected by RT-PCR after stimulation with autologous tumor cells. However, the cytotoxic activity of CTL8C2 was completely abolished when EGTA was added, suggesting that the cytolysis was mainly mediated by a Ca+2-dependent pathway, perforin/granzyme-based.
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PMID:The renal cell carcinoma lysis by a specific cytotoxic T cell clone is independent of the Fas/Fas-L cytotoxic pathway. 894 83

The CD95 (APO-1/Fas) system is an important mediator of T-cell cytotoxicity. We investigated this system in 22 hepatocellular carcinomas (HCCs) from patients. All HCCs had partially or completely lost the expression of the CD95 receptor constitutively expressed by normal liver cells and might thus evade CD95-mediated killing. We also considered a new mechanism of immune evasion, namely, the active destruction of T-lymphocytes by tumor cells expressing CD95 ligand (CD95L). CD95L messenger RNA and protein could be detected in the HCCs. In coculture experiments, HepG2 hepatoblastoma cells, expressing CD95L mRNA after treatment with cytostatic drugs, killed CD95+ Jurkat lymphocytes. Our data suggest that tumor cells can evade immune attack by down-regulation of the CD95 receptor and killing of lymphocytes through expression of CD95L.
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PMID:Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion? 905 44

This study investigates the effect of different cytokines on the growth and antitumor activity of the alpha CD3-induced killer cells CD3-AK, and the potential of the use of CD3-AK cells in cancer immunotherapy. Eight cytokines were tested. Only three (interleukin-2, -4 and -7) were able to support the growth of CD3-AK cells, which selectively killed different tumor targets of diversified origin. Culturing in interleukin-4 (IL-4) or IL-7 alone could maintain the growth of CD3-AK cells for 6-8 days. Only IL-2 could maintain long-term growth, but further addition of IL-4 exerted an inhibitory effect, which terminated the cell growth in 2 weeks. In contrast, despite the fact that IL-7 inhibited the proliferation of CD3-AK cells cultured in IL-2, as determined by [3H]thymidine uptake, the recovery of viable cells was not reduced. In 10 days, CD3-AK cells cultured in IL-2 alone or IL-2 plus IL-7 increased 160- or 176-fold respectively. There is an inverse relationship between the in vitro growth ability and Fas expression on the CD3-AK cells. Further, IL-7 increased the cytolytic activity of the CD3-AK cells two- to threefold. CD3-AK cells could be maintained in IL-2 or IL-2 plus IL-7 for 60-240 days or more. The long-term-cultured CD3-AK cells not only possessed a high level of cytolytic activity, but also showed a wide spectrum of killing with different tumor targets; the normally "resistant" targets, such as EL-4 lymphoma, fibrosarcoma, or melanoma, became susceptible. When the in vivo antitumor activity of the CD3-AK cells against a non-immunogenic tumor. EL-4, was tested by tumor-neutralization experiments, we found that only the long-term-cultured cells gave significant protection, with those maintained in both IL-2 and IL-7 giving the highest degree of protection. Thus, these long-term-cultured CD3-AK cells may have the potential to be used for immunotherapy of a variety of tumors whatever their immunogenicity.
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PMID:Interleukin-2 and interleukin-7 augment the cytolytic activity and expand the antitumor killing spectrum of alpha CD3-induced activated killer cells: potential use in the immunotherapy of non-immunogenic tumors. 902 5

Some chemotherapeutic agents, as well as TNF and Fas, induce apoptotic cell death in tumor cells, but the cellular components involved in the process have not yet been identified. Interleukin 1 beta converting enzyme (ICE) is a mammalian homolog of CED-3, a protein required for programmed cell death in nematode Caenorhabditis elegans. We found that a selective inhibitor of ICE/ced 3 family proteases, benzyloxycarbonyl Asp CH2OC(O) 2 6,-dichlorobenzene (Z-Asp-CH2-DCB). completely blocked the apoptotic cell death of human leukemia cells caused by etoposide, camptothecin, 1-beta-D-arabinofuranosyl cytosine (Ara-C) and adriamycin. Moreover, in antitumor agent-treated U937 cells, an ICE-like (CPP32-like) protease was strongly activated. These results indicate that ICE/ ced 3 family proteases are involved in antitumor agent-induced apoptosis. Activation of ICE family proteases plays a key role in apoptosis. However, the subsequent mechanisms resulting in apoptosis are largely unknown. We identified actin as a substrate of ICE family proteases. Cleavage of actin and other substrate proteins by ICE family proteases could be critical in the ongoing process of antitumor agent-induced apoptosis in tumor cells.
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PMID:[Involvement of ICE/CED 3 family proteases in antitumor agent-induced apoptosis]. 903 Feb 33

The elimination of tumor cells by cytotoxic T lymphocytes (CTLs) is, in part, executed by inducing apoptosis through the cell surface antigen Fas on the target cells. There are many cancer cells that resist Fas-mediated apoptosis. To elucidate the mechanism of this resistance is very important to understand the process of tumor development. We focused on FAP-1 (Fas-associated phos phatase-1), a negative regulator of Fas-mediated apoptosis. The expression of FAP-1 was detected in many colon cancer cell lines. On the other hand no FAP-1 expression was detected in the normal colon tissue. We have found that the tri-peptide of Fas C-terminus inhibited the binding of Fas and FAP-1 in vitro. Microinjection of the tri peptide (Ac SLV) could induce Fas-mediated apoptosis in the DLD 1 human colon cancer cell line that was resistant to anti-Fas-antibody. These findings suggest that the interaction of Fas and FAP-1 has a very important role in Fas-mediated apoptosis signal transduction. The inhibition of the Fas/ FAP-1 binding will provide a good target to develop anti-cancer drugs.
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PMID:[Development of anti cancer drugs targeted on Fas-mediated apoptosis signal]. 903 Feb 35

5H7, an anti-human class I MHC mAb that recognizes a monomorphic determinant of the alpha3 domain, profoundly inhibits T lymphocyte activation. The present study was designed to determine the role of programmed cell death in 5H7-mediated immune suppression. Incubation of PBMC with 5H7 mAb induced a marked reduction in viable cell recovery (VCR) of T cells (<10% VCR), NK cells (<1% VCR), and B cells (<1% VCR). In addition, 5H7 inhibited proliferation and VCR of JY, DBS-521, and BevD tumor lines as well as cells transfected with HLA-B27. Morphologic changes characteristic of apoptosis were induced by 5H7, including cell membrane blebbing, cytoplasmic vacuolization, condensation of nuclear chromatin, and nuclear fragmentation. Furthermore, DNA fragmentation was demonstrated in 5H7-treated PBMC using a TdT-mediated end-labeling (TUNEL) technique. 5H7, but not anti-Fas mAb, induced apoptosis of cell lines derived from patients with Niemann-Pick disease that lack acidic sphingomyelinase activity. In addition, induction of cell death by 5H7 was not inhibited by IL-1beta-converting enzyme (ICE) inhibitors under conditions that fully suppressed Fas-mediated apoptosis. These findings suggest that signal transduction through "classical" human class I MHC molecules induces apoptosis by a Fas-independent pathway that does not require acidic sphingomyelinase, is independent of ICE protease, and may represent a unique pathway of cell death in human lymphocytes.
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PMID:Anti-human class I MHC antibodies induce apoptosis by a pathway that is distinct from the Fas antigen-mediated pathway. 903 61

Activation of ICE/Ced-3 family proteases (caspases) has been proposed to mediate both the granule exocytosis and Fas-Fas ligand pathways of rapid target cell death by cytotoxic T lymphocytes. In agreement with this model, two peptide fluoromethyl ketone caspase inhibitors and baculovirus p35 blocked apoptotic nuclear damage and target cell lysis by the CTL-mediated Fas-Fas ligand pathway. The peptide caspase inhibitors also blocked drug-induced apoptotic cell death in tumor cells. In contrast, the caspase inhibitors blocked CTL granule exocytosis-induced target apoptotic nuclear damage, but did not inhibit target lysis. These results are consistent with recent demonstrations that granzyme B can activate caspases leading to apoptotic nuclear damage, but show that target cell lysis by CTL granule exocytosis occurs by a caspase-independent pathway.
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PMID:Target cell lysis by CTL granule exocytosis is independent of ICE/Ced-3 family proteases. 904 42

Killer lymphocytes are primary immune effectors of virus, certain bacteria, and tumor immunity and play a role in autoimmunity and transplant rejection. This article reviews progress in deciphering the mechanisms by which they kill target cells through induction of apoptosis by either the secretory, perforin/granzyme-based pathway or the nonsecretory pathway, (i.e., by triggering the cell-surface death receptor Fas (CD95) by the membrane-bound Fas ligand of the killer).
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PMID:Killing mechanisms of cytotoxic lymphocytes. 905 Mar 77

Angiogenic and poorly angiogenic tumor variants were obtained by an intraperitoneal inoculation of cells from clones of polyoma-virus transformed BALB/c 3T3 cells into syngeneic mice. The angiogenic tumor cells expressed a higher tumorigenicity phenotype and a higher capacity to produce artificial pulmonary metastases than cells from the poorly angiogenic tumors. The former cells expressed also significantly higher levels of the lymphocyte activation protein Ly-6E.1 than the former cells. The two types of cells did not differ in expression levels of CD44 and of a polyoma-virus specific membrane antigen. These results raise the possibility that the angiogenic phenotype is coregulated with Ly-6. The effect on Ly-6 expression of signal transduction through TNF receptors, functioning as pivotal regulators of angiogenesis was therefore studied. It was found that TNFalpha and more so antibodies against Fas down-regulate expression levels of Ly-6. This down-regulation seemed to be selective as expression levels of CD44 were not affected by this treatment.
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PMID:TNFalpha and anti-Fas antibodies regulate Ly-6E.1 expression by tumor cells: a possible link between angiogenesis and Ly-6E.1. 905 80

It is well established that target cell lysis by MHC class I-restricted CD8+ T cells is an important defense mechanism during infections with intracellular pathogens or against tumor targets. On the other hand, little is known about the physiologic role and the mechanisms of cytotoxicity of CD4+ MHC class II-restricted T cells. We have recently demonstrated that human autoreactive CD4+ T cells specific for one candidate autoantigen of multiple sclerosis, myelin basic protein, can mediate cytotoxicity. In the present report, we analyze the cytolytic mechanisms employed by these cells. We show that individual T cell clones, regardless of their cytokine phenotype, can be noncytotoxic or lyse target cells via either perforin- or Fas/Fas ligand-mediated cytotoxicity.
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PMID:Human autoreactive CD4+ T cell clones use perforin- or Fas/Fas ligand-mediated pathways for target cell lysis. 905 10


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