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)

The ability of the VQGEESNDK synthetic peptide corresponding to fragment 163-171 of human IL-1 beta to trigger lymphokine-activated tumor inhibition (LATI) of a poorly immunogenic fibrosarcoma (CE-2) of BALB/c mice was compared to that of the whole IL-1 beta. Neither molecule inhibits in vitro proliferation of CE-2 cells. Administration at the tumor challenge site for 10 days of daily injections of 50 micrograms of peptide 163-171 induce a consistent, although limited, inhibition of tumor growth, whereas similar injections of 1 pg of IL-1 beta induced a more marked LATI. However, strong LATI was elicited when these injections were performed in mice challenged with tumor cells admixed at 1/10 cell ratio with nonreactive lymphocytes from CE-2-bearing mice. The L3T4+ lymphocyte subset is mainly responsible for this enhancement. This reaction is abolished when recipient mice are sub-lethally irradiated, treated with cyclosporin A, or when the reactivity of L3T4+ and asialo GM1+ cells is suppressed. A similarly efficient LATI is found on combining the daily peptide injections with that of 10 U of IL-2. LATI stemming from this association, too, is abolished when mice are irradiated or treated with anti-L3T4 antibody, whereas it is not affected by cyclosporin A or anti-asialo GM1 antibody. Finally, a tumor-specific immune memory is acquired by about 50% of mice after LATI induced by IL-1 beta or 163-171 peptide alone and by about 80% of mice after LATI induced by peptide and lymphocytes from tumor-bearing mice or peptide and IL-2. These findings could lead to the building of a molecularly defined system to induce efficient immune recognition of tumor cells by using a peptide that does not cause any of the several inflammation-associated changes induced by the whole IL-1 beta.
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PMID:Lymphokine-activated tumor inhibition in mice. Ability of a nonapeptide of the human IL-1 beta to recruit anti-tumor reactivity in recipient mice. 246 12

Lymphokine-activated killer (LAK) cells have been defined as interleukin 2 (IL-2)-activated cytolytic effector cells exhibiting non-MHC restricted killing against a wide range of NK-sensitive and NK-resistant tumor cells. There has been considerable debate as to whether LAK cells are derived from NK cells or from a unique precursor population. In the present study, we compare LAK cells derived from T-cell-depleted nylon-wool-non-adherent spleen cells with endogenous NK cells and NK cells activated with the interferon inducer polyl.C., in terms of their phenotype and functional characteristics. The predominant splenic LAK precursor in the mouse was found to be a nylon-wool-non-adherent, thy1-, MICG-, J11d.2-, asialo GM1+ cell. This phenotype is shared by endogenous NK cells. A significant number of activated NK cells express macromolecular insoluble cold globulin (MICG) in addition to asialo GM1. Neither endogenous nor activated NK cells express a heat-stable antigen found on bone-marrow cells, immature T cells, and most B cells and defined by monoclonal antibody (MAb)J11d.2. However, J11d.2 is expressed on some LAK precursor and effector cells. The asialo GM1 marker is common to all LAK effector cells, while many are also thy1+, and/or MICG+. LAK effector cells are therefore a heterogeneous population sharing some phenotypic characteristics in common with NK cells. In addition, there is a positive correlation between LAK and NK activity in "high NK" and "low NK" mouse strains, suggesting that NK cells and LAK cells share a common lineage. Monoclonal antibodies to the alpha and beta chains of LFA-I inhibit LAK and activated NK function, while endogenous NK and CTL killing is affected only by anti-alpha chain antibodies. LAK cells, like MHC-restricted and non-restricted CTL clones, express mRNA transcripts of the C11 serine protease gene. We conclude that LAK cells share several features in common with cells of the NK lineage and may therefore represent NK cells in a unique state of activation. LAK cells appear to employ cytolytic machinery common to other lytic cell types.
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PMID:A functional and phenotypic comparison of murine natural killer (NK) cells and lymphokine-activated killer (LAK) cells. 246 57

This investigation was undertaken in order to assess both the preventive and antiproliferative effects of tumor necrosis factor (TNF) in a hepatic metastasis model, by means of inoculation of mouse colon-26 tumor cells into the portal vein via the superior mesenteric vein in male CDF1 mice, aged 5 weeks. Continuous 10-day administration of natural human TNF-alpha (nHuTNF-alpha) following the tumor cell inoculation caused no reduction but rather an increase in the number of hepatic metastases. However, pretreatment with this preparation daily for 10 days before the inoculation caused a remarkable decrease in the number of hepatic metastases. This prophylactic effect was reversed by the intravenous administration of anti-asialo GM1 antibody 24 h before the inoculation. The result of immunoperoxidase staining of liver specimens suggested that organ-associated natural killer cells might play a role in the metastatic inhibition. An apparent antiproliferative effect on metastatic liver tumors was also recognized following injection of nHuTNF-alpha from the 10th day after the inoculation. Thus, TNF appears to have important effects upon the host immune system, acting against liver metastases.
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PMID:Preventive and antiproliferative effects of tumor necrosis factor against experimental hepatic metastases of mouse colon-26 tumor. 250 Dec 53

The present study examines clonal variations in NK sensitivity in a methylcholanthrene-induced fibrosarcoma. Previous studies of clones from this tumor have shown considerable heterogeneity in H-2 expression, and an association between deleted or low levels of class-I products and increased tumorigenicity after subcutaneous implantation in immunocompetent syngeneic mice. Here, fibrosarcoma clones with no or low expression of MHC-class-I products were found to be sensitive to NK-mediated lysis, while clones with high levels of MHC-class-I expression were relatively resistant. One H-2+ (G2) and one H-2- (B9) clone were chosen for more detailed studies. Cold-target competition assays and conjugate cytotoxicity assays in agarose showed that splenic effector cells bound equally well to the H-2+ and H-2- tumor clone, although only the latter was sensitive to NK cell lysis. Treatment with 50 U/ml of rIFN-gamma for 48 hr increased the levels of H-2 expression and made both clones more resistant to NK-mediated lysis. In vivo studies with radiolabelled tumor cells showed that cells from the H-2+ clone survived better than cells from the H-2- clone in the pulmonary capillary bed after i.v. inoculation. This difference disappeared in mice treated with anti-asialo GM1 serum, known to deplete NK cell activity.
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PMID:NK sensitivity and lung clearance of MHC-class-I-deficient cells within a heterogeneous fibrosarcoma. 250 53

To investigate the effect of interferon-gamma (IFN-gamma) on the immunotherapy, we used the autocrinically stimulated system in which a mouse IFN-gamma cDNA was transferred by infection with a chimeric retrovirus containing the IFN-gamma gene. First, we established a tumor specific CTL clone (E-4) against 203-glioma cells (a 20-methylcholanthrene induced mouse ependymoblastoma line of C57BL/6 mouse origin), and then transferred murine IFN-gamma cDNA into E-4 by using retroviral vector (pSVX(Mu gamma delta A]. Out of five gene-transferred subclones, E gamma-4, E gamma-5, E gamma-6, E gamma-7 and E gamma-9, two subclones (E gamma-6 and E gamma-9) constitutively produced 8- to 10-fold amounts of IFN-gamma as compared with the parental E-4. Moreover, these two subclones exhibited two to three times higher killing activity against 203-glioma than the parental cells. The enhancement of the killing activities was abrogated by an adequate addition of anti-IFN-gamma antibody. No alteration was seen after the gene transfer in cell surface phenotypes, Thy-1+, Lyt-1-, Lyt-2+3+ and asialo-GM1-. Fluorescence-activated cell sorter (FACS) analysis showed that the surface expression of major histocompatibility complex (MHC) Class I antigen, H-2Kb, of parental E-4 was augmented remarkably, and it was not altered by the IFN-gamma gene transfer, but the Class II antigen, I-Ab, was slightly enhanced on the two IFN-gamma-producing sublines. Since it is considered that in the vicinity of the constitutively IFN-gamma-producing CTL cells, tumor cells are exposed to a high concentration of IFN-gamma and may be stimulated to induce or enhance the expression of surface antigens including MHC antigens as well as tumor associated antigens in relation to immune recognition. The 203-glioma cells pretreated with IFN-gamma were more efficiently killed by both the parental E-4 and the gene-transferred sublines. It was thus suggested that the specific tumor killing activity of the gene-transferred CTLs was augmented by the constitutive production of IFN-gamma derived from the exogenous gene. As the next step, a mouse IFN-gamma cDNA was transferred into a neuroblastoma line C1300 of A/JAx mouse origin. Two infected subclones C gamma 3 and C gamma 22, were obtained as a low and a high producers, respectively. Both IFN-gamma gene transferred cells remained unchanged as regards in vitro cell growth, morphological appearance and differentiation antigen expression such as neurofilaments after the IFN-gamma gene transfer. On the other hand, expression of MHC Class I antigens of both subcloned lines was extremely augmented at the surface expression level as well as at the transcription level, re
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PMID:[A novel experimental approach to immunotherapy against malignant brain tumor with the mouse IFN-gamma gene transfer]. 250 89

To examine the influence of interferon gamma (IFN-gamma) on tumorigenicity, we established constitutively IFN-gamma-producing cell lines from a malignant mouse neuroblastoma, C1300, by retroviral transfer of a mouse IFN-gamma cDNA. The gene-transferred cells generally showed an enhanced high-level expression of the major histocompatibility complex class I antigens at the cell surface and the transcription levels, irrespective of their IFN-gamma-producing potential. Although in vitro cell growth of these cells was unaffected by the IFN-gamma production, their s.c. tumor growth in syngeneic A/J mice was dependent upon levels of IFN-gamma production; tumors induced by a low-producer line grew well at a rate similar to those induced by the parental one, but tumor growth of a high-producer line was strongly suppressed. This apparent tumor suppression was abolished by simultaneous i.p. injection of anti-Lyt2.2 and/or anti-IFN-gamma monoclonal antibodies, and subsequently large tumors of the high producer were generated. Anti-asialoganglioside GM1 antibodies allowed the high-producer line to induce a substantial but only transient tumor growth, whereas other antibodies, such as anti-Lyt2.1, anti-IFN-beta, and anti-activated macrophage, had no such effect. The mice immunized with the high-producer line were resistant to tumor growth of the parental cells but permitted another kind of A/J tumor line, Sa-1, to induce remarkable tumors. These results indicate that the reduced tumorigenicity of the IFN-gamma high-producer line was due to the augmented specific anti-tumor immunity, in which cytotoxic T lymphocytes seemed to play a decisive role, probably as a result of the immunomodulatory effects of the IFN-gamma derived from the tumor.
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PMID:Exogenous expression of mouse interferon gamma cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity. 251 80

IFN-beta was more active than recombinant interferon-alpha (rIFN-alpha) and interferon-gamma (rIFN-gamma) in a human renal cell carcinoma transplanted in nude mice. In 3 out of 5 mice, the tumor completely disappeared and viable tumor cells were not observed at a daily dose of 5 x 10(5) U/mouse. Combination with anti-asialo GM1 antibody did not influence the tumor growth inhibition by IFN-beta. Mononuclear cells around damaged cancer cells were found not to be macrophages. Although the role of mononuclear cells remained unknown, the antitumor activity of IFN-beta seemed to depend on its direct cellular action. IFN-beta may be a useful agent in some renal cell carcinomas.
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PMID:The antitumor effects of IFN- beta against human renal cell carcinoma in athymic nude mice. 251 76

Mice bearing large (greater than or equal to 3 g) metastatic and nonmetastatic Lewis lung carcinoma (LLC) tumors were studied to determine if the tumor variants differentially induced bone marrow versus splenic hematopoiesis and the appearance of hematopoiesis-associated immune suppressor cells. The metastatic LLC-C3 and nonmetastatic LLC-C8 tumors were equal in their stimulatory effects in vivo on both the number of bone marrow myeloid progenitor cells (CFU) and the appearance of bone marrow immune suppressor cells. In contrast, the tumor variants differed in their effects on the spleen, with the metastatic tumors causing a more pronounced increase in the number of nucleated cells and CFU, a reduced blastogenic responsiveness to concanavalin (Con-A), and an increased suppressor cell activity than nonmetastatic LLC-C8 tumors. The splenic suppressor cells of mice bearing large LLC-C3 tumors resembled the bone marrow suppressor cells which we previously described (Young et al.: Cancer Res. 47, 100, 1987) in that they were nonadherent to nylon wool, sensitive to treatment with L-leucine methyl ester, insensitive to treatment with complement and Thy-1.2, MG-1.2, asialo-GM1, or anti-IgM antibodies, and mediated their suppression through a mechanism which was only partially indomethacin sensitive. The stimulatory effects on hematopoiesis and suppressor cells by the LLC variant tumors may have been mediated by the tumor-derived colony stimulating factor (CSF) activities. Bone marrow cell proliferation and colony formation were stimulated in vitro by culture supernatants of metastatic LLC-C3 cells and, to a lesser degree, of nonmetastatic LLC-C8 cells. These colony-stimulating factor (CSF)-containing supernatants also induced normal bone marrow cells to become immune suppressive. In contrast, supernatants of only LLC-C3 cells, and not of LLC-C8 cells, stimulated in vitro growth of splenic CFU from LLC-C3-bearing mice; spleen cells from normal mice and from LLC-C8 bearers were unresponsive to supernatants of the LLC variants. These results suggest that CSF produced by either the metastatic LLC-C3 or the nonmetastatic LLC-C8 tumors could concurrently stimulate bone marrow hematopoiesis and the appearance of bone marrow suppressor cells. However, the metastatic LLC-C3 tumor cells, and not the nonmetastatic LLC-C8 cells, could also cause expansion of progenitor cells and hematopoiesis to the spleen and, consequently, induce the appearance in the spleen of hematopoiesis-associated immune suppressor cells.
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PMID:Differential induction of hematopoiesis and immune suppressor cells in the bone marrow versus in the spleen by Lewis lung carcinoma variants. 252 92

Spleen cells from C57BL/6J mice bearing Ehrlich carcinoma growing as a solid tumor show progressive unresponsiveness to concanavalin A (Con A) and lipopolysaccharide (LPS) mitogens. This is accompanied by striking spleen enlargement with marked hematopoietic activity. Lymphoproliferative assays of normal spleen cells in co-culture with tumor-bearing spleen cells (TBSC) show that: (a) TBSC contain non-specific suppressor cells able to abrogate both Con A and LPS responses, or mixed lymphocyte reaction, of normal spleen cells and (b) suppression by TBSC is MHC-unrestricted, non-prostaglandin-mediated and greatly enhanced by Con A supernatants. Suppressor cells associated with TBSC are large, low-density cells without markers of mature B or T lymphocytes or of the mononuclear phagocyte system. Most appear to be asialo-GM1-negative, as suppression was only partially inhibited by treatment with anti-asialo-GM1 and complement. Since NK activity is lacking in TBSC, our data strongly suggest that these "null" suppressor cells are related to the natural suppressor (NS) cells found described in normal bone-marrow and neonatal spleens, or induced in adult spleens by total lymphoid irradiation, graft-vs.-host disease, or cyclophosphamide treatment.
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PMID:Development of splenic natural suppressor (NS) cells in Ehrlich tumor-bearing mice. 252 8

The present study examined the effects of various treatments on the antiproliferative activity of mouse serum. Its activity was estimated against the growth of EL4 tumor cells and L929 cells and against splenic blastogenesis in culture. The activity varied among mouse strains tested and among individuals in any strain. However, normal outbred NIH Swiss mice showed the highest activity among the strains and the least variation among individuals. The activity of serum from NIH Swiss mice constantly decreased 7 or 14 days after an injection of 10(6) Ehrlich or sarcoma 180 tumor cells subcutaneously in the right-hind footpad, intradermally in the right side of the chest or into the palm. Other routes, such as intraperitoneal, intravenous in the tail vein, subcutaneous in the right side of the chest and intramuscular in the left thigh, however, hardly affected the activity. The activity also decreased 7 days after an injection into the footpad of a biological response modifier such as PSK or OK-432. The antiproliferative activity of mouse serum seem to depend on macrophages but not natural killer-cell activity, because treatment with silica but not anti-(asialo-GM1) antibody totally reduced the activity. The active fraction was heat-stable (100 degrees C, 30 min) and its molecular mass was 127-140 kDa.
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PMID:Effects of injection routes of growing tumors and PSK or OK-432 on antiproliferative activity of mouse serum. 253 48


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