Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A subpopulation of human lymphocytes bearing receptors for the Fe portion of IgG causes lysis of nucleated target cells in the presence of antibody. The reaction is known as antibody-dependent cellular cytotoxicity (ADCC) and the effector cells have been called killer (K) cells. We have measured K cell activity quantitatively in the peripheral blood of cancer patients using 51Cr labeled murine mastocytoma target cells and hyperimmune rabbit antimastocytoma antibody. ADCC was the same in males and females, was not affected by eating, smoking or the presence of infections, but was decreased in those over 65 years, during pregnancy, and in those with cachexia, or severe sepsis associated with nonmalignant diseases. It was normal in those with cancers being treated for cure and in those with benign diseases, but was decreased in those with advanced cancers. Operation did not produce a significant change in those who were not immunodepressed; in those who were immunodepressed before operation it caused a significant decrease maximal by the fifth day with recovery by the 15th day. Radiotherapy caused a decrease in K cell activity, maximal at 4 weeks, that persisted for 12 weeks with recovery after that time in those who did not have residual tumor. The values did not return to normal in those who had persistent tumor or distant metastases.
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PMID:Effect of operation and radiotherapy on antibody-dependent cellular cytotoxicity. 31 42

DBA/2 mice were treated with four successive subcutaneous injections of rabbit anti-theta-gamma-globulin followed by the subcutaneous implantation of chemically induced mastocytoma (P-815-X2). Another series of animals received rabbit anti-thymus-gammaglobulin according to the same schedule and still another series of animals served as non-treated controls. A definite augmentation of the tumor growth, as evidenced by the dissemination of the tumor into the spleen, liver and kidney, was evident in the globulin-treated series. Such dissemination was not observed in the control animals, where the metastases were limited to the reginal lymph nodes. The studied gammaglobulins were different in two important respects; the death rate of animals and the frequency of thymic metastases were higher in the anti-theta-globulin series. These findings advocate the conclusion that anti-theta-globulin, prepared against the brain tissue, is the more specific and more potent T-lymphocyte suppressor of these two globulins studied. T-lymphocyte population seems to play an important role in host resistance against experimental neoplasia.
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PMID:The influence of anti-theta-globulin treatment on the growth of mastocytoma in mice. 41

Mycobacterial ribonucleic acid (RNA) and cell wall skeleton fraction isolated from H37Ra caused P-815 mastocytoma regression in DBA/2 mice provided the animals were presensitized with freshly harvested living H37Ra cells. In the absence of presensitization, only the RNA fraction inhibited. Cell wall skeleton fraction, under these conditions, stimulated tumor growth. Cell wall lipids (from H37Ra) added to H37Ra cell wall skeleton fraction did not increase the inhibitory activity of cell wall skeleton fraction alone. Mycobacterial RNA appeared to be an effective inhibitor of P-815 mastocytoma metastases as shown by (i) the inhibition of a second footpad lesion distant from the one treated and (ii) increase in survival time.
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PMID:Mycobacterial ribonucleic acid: comparison with mycobacterial cell wall fractions for regression of murine tumor growth. 82 69

Spontaneous human lymphocyte-mediated cytotoxicity (SLMC) against tumour-cell targets was examined in a series of patients with localized or malignant disease, both treated and untreated, and patients with untreated chronic lymphocytic leukemia (CLL). The level of SLMC was assessed by means of two previously established assay systems; the xenogeneic assay involving the mouse mastocytoma line P815, and the allogeneic assay in which the human chronic myelogenous leukemia-derived line, K562, was used. The assay systems involve the use of Ficoll-Isopaque-separated, iron-plus-magnetism-purified lymphocytes in an overnight 51chromium release assay, and reflect the cytotoxic ability of human non-T, complement receptor-, Fc receptor-positive lymphocytes. In the present paper, lymphocytes from all normal donors tested showed significant activity in the SLMC assay, with some variation from day to day. This variation was markedly reduced when different normal donors were tested on the same day and under identical experimental conditions. In contrast, lymphocytes from many patients with malignant disease had decreased SLM activity, and this decrease was highly significant in patients with treated or untreated metastatic disease, or untreated CLL. This was also the case when the data were expressed relative to the number of cytotoxic cells in the normal control population, or in comparison to the relative SLMC activity of lymphocytes from patients with other conditions. Markedly decreased SLMC was observed in some patients in spite of normal T and B lymphocyte proportions, or the presence of the ability to mount a vigorous delayed hypersensitivity reaction to PPD. A comparison of the xenogeneic and allogeneic assays showed that the same information with respect to whether SLMC was normal or abnormal was obtained with both assays in the majority of cases. The significance of the data is discussed with respect to the possible role of SLMC in vivo and the relevance of SLMC to the assessment of specific cell-mediated cytotoxicity in malignant disease.
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PMID:Spontaneous human lymphocyte-mediated cytotoxicity againts tumour target cells. I. The effect of malignant disease. 82 77

The immunomodulatory and anti-tumor activity of Bru-Pel, an aqueous-ether extracted residue of Brucella abortus (strain 456), was investigated. Bru-Pel was administered to C57BL/6 mice intraperitoneally (i.p.) and tested for its effect on natural killer (NK) cell activity in spleen cells, liver, and peritoneal cavity. Three days after injecting 100 micrograms of Bru-Pel i.p., the cytotoxicity of spleen cells against YAC-1 target cells, assessed by LU20 increased by approximately two-fold and nonparenchymal cells of liver by greater than six-fold. The highest stimulatory effect of Bru-Pel was seen with peritoneal exudate cells, and 47-fold augmentation of NK cell activity was observed. Bru-Pel treatment made spleen, liver, and peritoneal exudate cells capable of lysing P815 mastocytoma cells, a tumor cell line highly resistant to lysis by unstimulated NK cells. In vivo, Bru-Pel inhibited the formation of experimental BL6 melanoma metastases; however, there was no significant effect on the eradication of established pulmonary metastatic lesions. These results demonstrate that in addition to its previously described macrophage-activating ability, Bru-Pel is highly efficient in stimulation of NK cell-mediated cytotoxicity in mice.
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PMID:Augmentation of natural killer cell activity in mice by Bru-Pel. 179 Jan 38

Kupffer cells (KC) are believed to play a major role in protecting the liver from metastases. In vitro, activated KC mediate both tumor cell cytostasis and cytolysis. Because hepatocytes (HC) occupy a position adjacent to KC in vivo, we investigated the influence of HC on KC tumoricidal activity. Using an in vitro assay of KC-mediated tumor cell cytostasis against murine P815 mastocytoma cells, we found that the presence of HC in the culture profoundly increased KC tumoricidal activity. HC enhanced KC inhibition of P815 proliferation and lowered the concentration of lipopolysaccharide and interferon-gamma necessary to activate the KC to a tumoricidal state. This stimulatory HC effect was dependent on the number of HC present and was transferable in cell-free supernatants, indicating that it was mediated by a soluble secreted product of HC. Furthermore, unlike other macrophage-priming or -potentiating factors, the transferable HC factor(s) was effective only if added simultaneously with lipopolysaccharide or interferon-gamma and not effective if added before these activating agents. These data show that HC produce a soluble mediator that enhances KC tumoricidal activity, suggesting that HC and KC interactions may be critical to the antitumor defense mechanisms of the liver.
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PMID:Hepatocytes enhance Kupffer cell-mediated tumor cell cytostasis in vitro. 250 99

The growth, phenotype, in vitro cytolytic characteristics, and in vivo antitumor activity of murine splenocytes stimulated with anti-murine CD3 mAb in combination with IL-2 as compared with IL-2 alone was investigated. When cultured for 12 days with anti-CD3 mAb + IL-2, murine splenocytes increased 100- to 4000-fold in number compared with only 6- to 20-fold for cultures stimulated with IL-2 alone. Anti-CD3 mAb + IL-2 activated cultures developed high lymphokine-activated killer activity against NK-resistant targets including the P815 mastocytoma cell line and fresh MCA 106 sarcoma. Peak cytotoxicity on a per cell basis developed by day 8 after anti-CD3 mAb + IL-2 activation. A large proportion of the total cytolytic activity of long term anti-CD3 mAb + IL-2-stimulated cultures was related to the presence of anti-CD3 in the assay, indicating enhancement of cytotoxicity by activated CD3+ T cells. Phenotypic analysis indicated that anti-CD3 mAb + IL-2-stimulated cultures contained heterogeneous populations of T cells with increased percentages of both CD4+ and CD8+ phenotypes compared with cultures stimulated with IL-2 alone. Anti-CD3 mAb + IL-2-stimulated cells were tested for their in vivo antitumor activity by using C57BL/6 mice bearing MCA 106 sarcoma pulmonary metastases. IL-2-activated murine killer cells were given in combination with in vivo IL-2 and indomethacin, the latter of which was shown to potentiate the antitumor effect of IL-2. When given on day 5 after tumor inoculation, cell doses as low as 5 x 10(6) anti-CD3 mAb + IL-2-stimulated cells per mouse significantly reduced the number of pulmonary metastases (p less than 0.005). Thus, activation with the combination of anti-CD3 mAb + IL-2 produces rapidly expanding cultures of cytolytic cells with demonstrated in vivo antitumor efficacy.
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PMID:Anti-CD3 + IL-2-stimulated murine killer cells. In vitro generation and in vivo antitumor activity. 252 62

If immunoregulation of cancer is to be effective, the tumor must express immunogenicity and the host immune mechanism must be capable of responding to that stimulus. Though neuroblastoma (NB) might be such a tumor, a systematic assessment of this complex host-tumor interaction is lacking. We report such an analysis using the murine NB system. C1300-NB is highly antigenic, locally growing, and nonmetastasizing, while its clonal counterpart, TBJ-NB, is minimally antigenic and demonstrates not only aggressive local growth but systemic metastases as well. We analyzed A/J mouse antitumor naturally occurring killer lymphocyte (NK cells), cytotoxic lymphocyte (CTL cells), and suppressor lymphocyte (SC cells) function in response to these tumor lines. NK and CTL activity was measured in 40 mice after 3 weeks of growth of either C1300-NB or TBJ-NB using a cold target inhibition test to either the YAC-1 or P815 mastocytoma cell line, respectively. SC activity was analyzed in an additional 24 mice treated with an SC destroying 15 mg/kg of cyclophosphamide (CYA) three days after tumor inoculation. After 4 weeks of tumor growth spleens were harvested, cell-mediated cytotoxicity was measured by chromium 51 release assay and tumor cell lysis was expressed as lytic unit 30 (LU-30), an arbitrary definition of the number of lymphocytes needed to lyse 30% of target cells. By increasing the concentration of the NK-sensitive YAC-1 cold target, there was a 56.8% inhibition of lymphocytotoxicity to C1300-NB, contrasting with this was the lack of inhibition (17.8%) by the non-NK sensitive P815 cell line.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Systematic analysis of the immunoregulation of murine neuroblastoma. 252 62

The role of the immune response in the elimination of spontaneous metastases arising from intraocular tumors was examined in a syngeneic intraocular murine tumor model. P91 mastocytoma (DBA/2 origin) expresses strong tumor-specific transplantation antigens and grows transiently in the eyes of syngeneic hosts before undergoing spontaneous rejection. An organ culture technique was used to detect spontaneous metastases in the lungs, spleens, brains, and thymuses of intraocular tumor-bearing mice. Metastatic tumor cells were detected in all organs of immunodeficient mice (i.e., athymic, nude, or x-irradiated DBA/2 mice) within 14 days of intraocular transplantation, and grew progressively thereafter. By contrast, metastatic tumors were rejected in 100% of the immunocompetent DBA/2 mice examined on day 15. Timed enucleation experiments demonstrated that the immune rejection of disseminated tumor cells occurred within 24-48 hr of their arrival at the various organs. The immune rejection of spontaneous metastases could be adoptively transferred to immunodeficient tumor-bearing mice using spleen cells, but not immune serum, from intraocular tumor-bearing immunocompetent donors. Selective cell depletion experiments revealed that the immune spleen cell effecting immunity was an Lyt 1+, 2+ T cell. The results indicate that the immune rejection of the spontaneous metastases arising from primary intraocular tumors is a T cell-dependent, radiosensitive process that rapidly eliminates metastases within the lungs, brain, thymus, and the spleen of the immunocompetent host.
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PMID:Immune rejection of metastases arising from intraocular tumors in mice. 309 27

Nocardia delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, injected i.p. in an oil/water emulsion to F6 rhabdomyosarcoma-bearing rats, inhibited the development of pulmonary metastases; 6 out of 10 rats were protected. Repeated i.p. administration of emulsified NDCM and of two other compounds, a Nocardia water soluble mitogen (NWSM a hydrosoluble fraction) and purified cell walls (CW, an insoluble macromolecular fraction) in Lewis lung carcinoma (LLC)-bearing mice resulted in a significant reduction of lung metastases. The efficiency of these fractions was enhanced by association with monokines. A combination regimen of NDCM, NWSM, and CW (100 micrograms/0.1 ml) and monokines (0.1 ml), injected i.p. in LLC-bearing mice, yielded a greater antimetastatic effect than either therapy alone. Peritoneal macrophages from mice which had been injected i.p. with NWSM or CW, when triggered either by TPA (tetradecanoyl phorbol acetate) or by zymosan, released large quantities of hydrogen peroxide and had a high rate of glucose consumption. These macrophages were activated as judged by their cytostatic activity against syngeneic P815 mastocytoma growth; they expressed biochemical markers which have been reported to characterize the activated state. Incubation of thioglycollate-elicited peritoneal macrophages with NWSM, and monokines for 72 h resulted in a cytotoxic activity against labeled LLC cells; addition of macrophage activating factor significantly increased the cytotoxic capacity of these macrophages. In view of this we postulate that the antimetastatic effect of soluble and insoluble N. opaca fractions and monokines might be mediated by activated peritoneal macrophages.
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PMID:Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by these fractions. 311 66


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