Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A subset of gastric carcinoma carries Epstein-Barr virus (EBV). The immunophenotypic features of EBV-associated (EBV+) gastric carcinoma, which we have analyzed using 25 EBV+ cases, remain unclear. Frozen tissue samples were stained with antibodies to various immune cell markers. To evaluate the proliferative activity of CD8+ cells, we performed CD8/Ki-67 double staining on paraffin-embedded sections. The results were compared with those in EBV-negative (EBV-) gastric carcinomas. All EBV+ and EBV- gastric carcinoma cells expressed major histocompatibility complex class I, whereas major histocompatibility complex class II expression in tumor cells was more prominent in EBV+ cases. Intercellular adhesion molecule-1 and Fas/APO-1 expression was largely restricted to EBV+ cases. The lymphocytes that infiltrated EBV+ tumor nests were predominantly CD8+ T cells, many of which expressed perforin. Immunoelectron microscopy confirmed a close cell to cell contact between these CD8+ cells and carcinoma cells. CD8+ cells were CD11a+ and CD11b- by flow cytometry performed in one case. The labeling index of Ki-67, the proliferation-associated antigen, in CD8+ cells was 4 times higher in EBV+ cases than in EBV- cases. Our data suggest that these CD8+ cells, which bear a cytotoxic phenotype, are actively proliferating in close contact with EBV+ tumor cells and that the specificity of the CD8+ cells may be directed to EBV and/or cellular antigens expressed by the tumor. This is consistent with a generally favorable prognosis of EBV+ gastric carcinoma. Because the observed T-cell infiltration is insufficient to eradicate the tumor cells, certain immunosuppressive factors were speculated to allow the essentially immunogenic carcinoma cells to establish a macroscopic lesion.
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PMID:Immunophenotypic characterization of Epstein-Barr virus-associated gastric carcinoma: massive infiltration by proliferating CD8+ T-lymphocytes. 868 41

Cytotoxic function of CD4+ Th1 cells is mediated by Fas (CD95, APO-1) and its ligand (Fas ligand). Recent studies using nontransformed B cells and the Ramos Burkitt's lymphoma (BL) B-cell line cells show that CD40 ligation at the B-cell surface by activated, CD40 ligand (CD40L)-bearing, CD4+ T cells upregulates Fas expression on B cells and primes B cells for Fas-mediated death signals. In this work, we examine whether this CD4+ T-cell-dependent molecular pathway for Fas upregulation and B-cell apoptosis reflects a peculiarity of the Ramos B-cell line or is applicable to other Burkitt's tumors as well. In 5 of the 6 Epstein-Barr virus-negative BL cell lines examined, the cells constitutively express undetectable or low levels of Fas and are resistant to Fas-mediated signals induced by monoclonal anti-Fas antibody. All 6 of the BL cell line B cells upregulate Fas in response to CD40 ligation, and in 4 of the cases they become sensitive to Fas-mediated death signals. In one BL cell line, the cells are constitutively sensitive to Fas-mediated cytolysis and are unaffected by CD40 signals. Next, we applied these immunologic manipulations to cells from a refractory clinical sample and observed that the tumor cells could be induced to express Fas and undergo apoptosis in our system. These results establish CD4+ T cells and the Fas-Fas ligand system as important immune regulators of Burkitt's lymphoma B cells and indicate that the susceptibility of tumor cells to Fas-mediated death signals can be modulated by specific activation events at the cell surface.
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PMID:CD4+ T-cell induction of Fas-mediated apoptosis in Burkitt's lymphoma B cells. 869 56

Studies with perforin-deficient mice have demonstrated that two independent mechanisms account for T cell-mediated cytotoxicity: A main pathway is mediated by the secretion of the pore-forming protein perforin by the cytotoxic T cell, whereas an alternative nonsecretory pathway relies on the interaction of the Fas ligand that is upregulated during T cell activation with the apoptosis-inducing Fas molecule on the target cell. NK cells use the former pathway exclusively. The protective role of the perforin-dependent pathway has been shown for infection with the noncytopathic lymphocytic choriomeningitis virus, for infection with Listeria monocytogenes, and for the elimination of tumor cells by T cells and NK cells. In contrast, perforin-dependent cytotoxicity is not involved in protection against the cytopathic vaccinia virus and vesicular stomatitis virus. LCMV-induced immunopathology and autoimmune diabetes have been found to require perforin-expression. A contribution of perforin-dependent cytotoxicity to the rejection of MHC class I-disparate heart grafts has also been observed. Its absence is efficiently compensated in rejection of fully allogeneic organ or skin grafts. So far, evidence for a role of Fas-dependent cytotoxicity as a T cell effector mechanism in vivo is lacking. Current data suggest that the main function of Fas may be in regulation of the immune response and apparently less at the level of an effector mechanism in host defense. Further analysis is necessary, however, to settle this point finally.
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PMID:Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo. 871 13

The mechanisms of cytotoxic killing of various tumor cell lines and immunodeficiency virus-infected T cell lines by simian gamma delta T cells were examined. The lysis of the majority of the target cell lines by gamma delta effectors was calcium-dependent, indicating that cytotoxicity is mediated by the perforin/granzyme pathway rather than the Fas-FasL pathway, with the exception of Jurkat cells. The gamma delta T cells were able to suppress SIV replication as measured by the p27 ELISA and the suppression was contact-dependent. We further determined that the target cells were induced to undergo apoptosis by the gamma delta T cell effectors. These results contribute to our understanding of the function of simian gamma delta T cells and their similarities to human gamma delta T cells, and extend our knowledge on the cytotoxic mechanisms employed by gamma delta T cells in general.
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PMID:Mechanisms of simian gamma delta T cell cytotoxicity against tumor and immunodeficiency virus-infected cells. 873 16

Fas (APO-1, CD95) is a type I integral membrane protein initially identified by mAbs that induce apoptotic cell death upon binding to certain tumor cells and its belongs to the TNFR family. Fas is expressed on activated lymphocytes and in various tissues including the liver, lung, intestine, and skin. Molecular cloning of Fas ligand (FasL) revealed that it is a type II integral membrane protein homologous to TNF. FasL is predominantly expressed on activated T and NK cells, and mediates Fas divided by target cell lysis by these effector cells. The Fas/FasL system has been also implicated in the pathogenesis of autoimmune diseases, fulminant hepatitis, GVHD, and AIDS. It has been recently reported that human FasL was released as a 26 kD soluble form from COS cells transfected with human FasL cDNA and activated human T cells. In this communication, metalloproteinase-mediated release of FasL and it's clinical relevance are discussed.
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PMID:[Metalloproteinase-mediated release of human fas ligand]. 874 61

Pim-1, a protooncogene product, induced tumor in the combination with MYC. So far, two reports were published concerning Pim-1 function to apoptosis. One was that Pim-1 inhibit apoptosis in Pim-1 introduced transgenic mouse with a background of lpr/lpr, in which Fas was abrogated. However, the other that Pim-1 induced apoptosis in a transient expression system was also reported. In this communication, we survey the possible functions of Pim-1 in terms of the factor related to apoptosis and carcinogenesis.
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PMID:[Apoptosis related gene, Pim-1]. 874 85

Treatment of drug-sensitive or resistant tumor cells with combination of anti-Fas antibody and drugs (e.g., CDDP) results in augmented cytotoxicity and synergy. This study examined a possible underlying mechanism of synergy achieved by anti-Fas and CDDP. Three human ovarian tumor cell lines were selected for the studies, namely, the CDDP-sensitive A2780 and CDDP-resistant variants AD10 and C30 tumor cells. All three lines express Fas but are resistant to cytotoxicity by anti-Fas antibody. Treatment of tumor cells with monoclonal mouse antihuman Fas (IgM) antibody and CDDP resulted in significant augmentation of cytotoxicity and synergy in all three lines. The magnitude of synergy was a function of the concentrations of both the anti-Fas antibody and the CDDP used. Pretreatment of tumor cells first with CDDP, but not with anti-Fas and then treatment with anti-Fas, resulted in synergy, suggesting that CDDP sensitizes the cells to anti-Fas-mediated cytotoxicity. This was corroborated by inhibiting synergy by the addition of neutralizing anti-Fas (IgG) antibody. Sensitization of tumor cells by CDDP resulted in upregulation of surface Fas expression which was dependent on de novo protein synthesis. Findings similar to those obtained in cytotoxicity were also obtained in apoptosis as determined by DNA hypoploidy and DNA fragmentation. The effect of CDDP-mediated sensitization to anti-Fas and cytotoxicity was compared to CDDP-mediated toxicity. The addition of the antioxidant butylated hydroxyanisole (BHA) inhibited CDDP-mediated cytotoxicity in both AD10 and C30 but not in A2780 ovarian tumor cells. However, BHA did not inhibit upregulation of Fas expression by CDDP in all three lines and further BHA did not inhibit the synergy achieved with combination of subtoxic concentrations of CDDP and anti-Fas (IgM) antibody. These findings revealed that CDDP exerts its cytotoxic effect and its sensitization to Fas cytotoxicity by different mechanisms. Since cytotoxic T lymphocytes (CTL) express Fas ligand and kill Fas+ target cells, a significant potentiation of tumor cell killing will be achieved following sensitization of tumor cells to Fas signaling by subtoxic concentrations of CDDP. These findings suggest a new approach for augmenting CTL-mediated immune interventions in the therapy of resistant ovarian tumor cells.
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PMID:Sensitization of human ovarian tumor cells by subtoxic CDDP to anti-fas antibody-mediated cytotoxicity and apoptosis. 875 62

Fas is a widely expressed membrane-anchored protein that induces apoptosis. Soluble Fas (sFas), generated by alternative mRNA splicing, can antagonize cell-surface Fas function. We have investigated sFas in 104 cancer patients with nonhematopoietic malignancies using a Fas-specific ELISA and immunoprecipitation. Our studies demonstrate an elevated 40-42-kDa sFas species in both patient serum and tumor explants. These observations provide the first evidence that sFas is increased in patients with solid tumors in a manner reflective of disease stage and tumor burden and argue that sFas can be synthesized and released both systemically and locally within the tumor microenvironment.
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PMID:Elevated soluble Fas (sFas) levels in nonhematopoietic human malignancy. 875 48

CD95 (APO-1/Fas) is a member of the superfamily that includes the nerve growth factor and tumor necrosis factor receptors, OX40, CD27, CD30, and CD40. Present on a minority of resting blood lymphocytes, CD95 expression is upregulated on activated T and B lymphocytes and natural killer cells, where binding of the antigen by anti-Fas and anti-APO-1 antibodies has been shown to induce apoptosis. This CD95-mediated apoptosis is at least partially inhibited by expression of the Bcl-2 protooncogene. To evaluate possible roles of CD95 and Bcl-2 in growth regulation of lymphoid neoplasms, we studied by immunohistochemistry the expression of CD95 and Bcl-2 in 67 B- and 5 T-cell lymphomas, and 10 cases of Hodgkin's disease. In all, 29 B and 2 T cell lymphomas, and 9 cases of Hodgkin's disease expressed CD95. Compared with diffuse large B-cell and Burkitt-like lymphomas, lowgrade B-cell lymphomas more frequently expressed CD95 (52% versus 26%; P < .005). None of the B-cell small lymphocytic lymphomas or mantle cell lymphomas expressed CD95, whereas the majority of follicle center lymphomas, extranodal marginal zone B-cell lymphomas, and immunocytomas were CD95+. Of the 29 CD95+ B-cell lymphomas, only 33% of the high-grade group coexpressed Bcl-2, compared with 87% of the low-grade group (P < .04). Two of three peripheral T-cell lymphomas--including one anaplastic large cell lymphoma--expressed CD95. Staining for CD95 was seen in 9 of 10 cases of Hodgkin's disease. The infrequent expression of CD95 in high-grade B-cell lymphomas suggests an association between loss of CD95 expression/function and a more aggressive tumor grade. Whereas frequent coexpression of Bcl-2 with CD95 may protect low-grade B-cell lymphomas against CD95-mediated apoptosis, in the high-grade group such coexpression is infrequent, and other regulators besides Bcl-2 may be involved in modulating the apoptosis signal delivered by CD95.
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PMID:Expression of CD95 antigen and Bcl-2 protein in non-Hodgkin's lymphomas and Hodgkin's disease. 877 39

Fas/APO-1 is a cell-surface protein, a member of the TNF-receptor family, and it potentially induces apoptosis. In presence of an apoptosis-inducible anti-human Fas MAb, Fas-negative control PC-3 human prostate-cancer cells did not undergo morphological changes, while PC-3 human Fas transfectants showed apoptotic changes in vitro. However, LNCaP human Fas transfectants, as well as Fas-negative control LNCaP human prostate-cancer cells, were Fas-resistant. The growth of Fas-transfected PC-3 tumor was retarded compared with that of control PC-3 tumor in vivo without stimulation of anti-human Fas MAb. Anti-human Fas MAb administration in vivo caused macroscopic Fas-transfected PC-3 tumors formed in BALB/c nude mice to undergo apoptosis.
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PMID:Modulation of growth and apoptosis response in PC-3 and LNCAP prostate-cancer cell lines by Fas. 878 63


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