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

The cell-mediated immune response against a transplantable syngeneic metastatic solid tumor in mice was studied. The immune reactivity of spleen cells from tumor-bearing mice was found to vary during development of the tumor. For about a week after tumor transplantation, the spleen cells were able to protect recipient mice against challenge with tumor cells. Subsequently, the protective activity was replaced by an enhancing activity. Recipient mice that received tumor cells together with spleen cells from mice bearing tumors for about two or three weeks had a higher incidence of tumor takes and larger tumors than controls. This enhancement of tumor development was correlated with the size of the local tumor or metastases in the donors. The enhancing activity was found to be mediated by T lymphocytes and appeared to suppress the protective immune response of the recipients. We devised a system to strengthen the immune response of the host against the development of tumor metastases. In the tumor model used, removal of the local tumor after s.c. transplantation failed to prevent the development of lung metastases and death in most of the mice. However, syngeneic spleen cells which had been sensitized in vitro against tumor cells were found to serve as immunotherapeutic agents. Injection of such spleen cells into mice from which primary tumor implants had been removed surgically led to a markedly increased survival. Spleen cells from both normal and tumor-sensitized donors were effective, but splenocytes from mice bearing large tumors did not reduce metastatic development after sensitization in vitro. Thus, protection against the development of lethal metastases can be achieved with certain types of lymphocytes sensitized in vitro.
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PMID:A syngeneic metastatic tumor model in mice: the natural immune response of the host and its manipulation. 108 80

The transplantable rat kidney carcinoma (RKC) provides an excellent experimental model for immunological and therapeutic studies of renal cell carcinoma. In this report, we define the biological characteristics of RKC and explore the interactions between RKC and natural killer (NK) cells. RKC, a transplantable tumor of spontaneous origin, grows progressively over a 12-week period and metastasizes to the lung when implanted orthotopically in the kidneys of female Lewis rats. Rats bearing RKC survived for an average of 10.5 +/- 1.5 (SD) weeks postimplantation. Lung metastases were visible between 7.5 and 8.5 weeks postimplantation, and by 9 to 10 weeks the incidence of metastases reached approximately 67%. Injection of the NK cell-specific monoclonal antibody 3.2.3 depleted Lewis rats of their NK activity for up to 14 days. Adherent lymphokine-activated killer cells generated from the spleens of 3.2.3-injected rats were significantly less lytic than those from control rats and contained a significantly lower percentage of 3.2.3+ cells when analyzed by flow cytometry. Groups of rats were implanted with RKC and received injections of 3.2.3 biweekly to maintain depletion of NK cells or of a control antibody, NK1.1, specific for mouse NK cells. At 10 weeks postimplantation, 3.2.3-injected rats had significantly (P < or = 0.005) larger tumors (104.4 +/- 20.1 g) than NK1.1-injected rats (75.4 +/- 13.9 g). Spleen cells and peripheral blood cells from uninjected, tumor-bearing rats had a slight but nonsignificant decrease in NK activity against 51Cr-labeled YAC-1 targets over the course of RKC progression. The activity of adherent lymphokine-activated killer cells from tumor-bearing rats was lower than that from normal rats, but not significantly. Cultured RKC cells were killed by both splenic NK cells and adherent lymphokine-activated killer cells. These data demonstrate that RKC is NK sensitive and that tumor growth does not abrogate NK activity. The RKC tumor provides a model system for the analysis of immunological factors in renal cell carcinoma growth and presents opportunities for testing therapeutic interventions in a system that closely mimics the human disease.
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PMID:Renal cell carcinoma and natural killer cells: studies in a novel rat model in vitro and in vivo. 142 74

The number of spontaneous lung metastases and the frequency of metastasis formation in the lymph nodes of mice were studied following the induction of tumour growth by injection of tumour cells. A syngeneic transplantable mammary adenocarcinoma, MMT 1, from C3H/He mice, and a cloned strain, MMTV4, obtained by treating MMT1 cells with 5-azacytidine in vitro, were used. No differences between MMT1 and MMTV4 were detected in the number of spontaneous metastases in the lungs of mice. An in vitro cytotoxic test and an adoptive transfer test were used to measure cytotoxic activity and the antimetastatic activity of spleen macrophages. The macrophages from mice bearing the MMT1 tumour exhibited antimetastatic activity in the adoptive transfer test, and specific and nonspecific cytotoxic activity in the in vitro test. Macrophages from mice carrying the MMTV4 tumour possessed nonspecific cytotoxic activity in vitro but did not exhibit antimetastatic activity in the adoptive transfer test. Tumours were surgically removed 13-15 days after their induction. Two weeks after the MMT1 tumour was resected, an abrupt increase in the number of spontaneous metastases in the lungs and in the lymph nodes was observed, whereas after removal of the MMTV4 tumour there were no changes in the number of lung metastases. When mice with the MMT1 tumour were given the cyclooxygenase inhibitor, indomethacin, in their drinking water, there was a significant decrease in the number of spontaneous lung metastases. Spleen macrophages from mice operated on after injection with MMT1 or MMTV4 did not possess specific cytotoxicity in the in vitro test.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Participation of macrophages in the mechanism mediating the enhancement of metastasis formation after tumour resection. 184 24

Different spleen and tumor cell factors modifying tumoral and metastatic growth were studied. Spleen cell culture supernatants (SCS) from small and large tumor-bearing mice enhanced tumor growth. After tumor surgery, tumor enhancement was only mediated by supernatants from large tumor resected mice. Tumor facilitation and angiogenic response were mediated by the same supernatants; different fractions for these two activities were characterized. T and non-T cells, depending on tumor burden, were responsible for the enhancing activity; but angiogenesis depended only on T cells. While augmentation of metastatic spread was produced by tumor antigens (soluble tumor extracts, tumor-cell supernatants, formolized tumor cells), primary tumor development was not modified by tumor-cell supernatants. Increased incidence of metastases was also mediated by SCS from tumor resected mice which had previously been inoculated with tumor antigens. Immune status of tumor-resected mice was evaluated by delayed-type hypersensitivity reaction. Tumor cell membranes enriched with cholesterol-hemisuccinate were able to increase anti-tumor immune response.
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PMID:[Immunoregulation of tumor growth in a murine model]. 248 20

Killer helper factor (KHF) was previously found to be produced by a human T cell hybridoma, 24A . CA2. We studied the therapeutic effects of interleukin-2 (IL-2) and KHF on the inhibition of pulmonary metastases of syngeneic Lewis lung carcinoma (3LL) in C57BL/6N mice. Multiple subcutaneous (sc) injections of IL-2 plus KHF had significantly more effect than injections of IL-2 alone in inhibiting spontaneous pulmonary metastases and prolonging survival of the mice. The effect of KHF with IL-2 on induction of lymphokine (IL-2)-activated killer (LAK) activity against P-29 cells was examined in the murine system. Spleen cells generated LAK activity after incubation for 4 days with more than 500 U/ml of IL-2. In contrast, KHF alone did not render spleen cells cytotoxic. The combination of these lymphokines at subthreshold concentrations, however, resulted in significant in vitro induction of LAK activity. The LAK activity of splenocytes incubated with IL-2 plus KHF was maximal after 4 days, and persisted for longer than that of cells treated with IL-2 alone. The LAK cells induced by KHF plus IL-2 were also cytotoxic to FBL and YAC-1 cells. Moreover, spleen cells of mice bearing lung metastases could be induced to the cytotoxic state by sc injections of IL-2 plus KHF. These results indicate that combination treatment with IL-2 and the new lymphokine KHF should be useful clinically in inducing LAK activity for inhibition of pulmonary metastases.
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PMID:Enhancement of therapeutic effect of interleukin-2 on spontaneous pulmonary metastases of Lewis lung carcinoma by killer helper factor associated with increased induction of killer activity. 250 76

Spleen cells of C57BL/6N mice bearing lung metastases were induced to the cytotoxic state by subcutaneous injection of recombinant human interleukin-2 (IL-2) at a minimum dose of 5 x 10(4) U/mouse three times a day for 3 consecutive days. A single intraperitoneal injection of lentinan alone at concentrations of up to 10 mg/kg body weight did not render spleen cells cytotoxic to P-29 cells, but a combination of subthreshold doses of these agents (5 x 10(4) U/ml IL-2 and 5 mg/kg lentinan) induced significant in vivo lymphokine-activated killer activity in spleen cells of tumor-bearing mice. Similarly, spleen cells from mice treated i.p. with lentinan became cytotoxic on in vitro treatment with IL-2. The in vitro responsiveness of spleen cells to IL-2 was maximal 3 days after i.p. injection of lentinan. Synergism between IL-2 and lentinan was also observed in mice bearing spontaneous lung micrometastases: neither IL-2 (less than 5 x 10(4) U/mouse) nor lentinan (less than 2.5 mg/kg) alone had a therapeutic effect, but multiple injections of IL-2 with a single injection of lentinan resulted in significant inhibition of spontaneous pulmonary metastases. From these results we conclude that IL-2 and lentinan in combination are more effective than either one alone for inducing destruction of pulmonary metastases.
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PMID:Synergistic induction of lymphokine (IL-2)-activated killer activity by IL-2 and the polysaccharide lentinan, and therapy of spontaneous pulmonary metastases. 278 52

The MC-2 fibrosarcoma, which is a transplantable tumour syngeneic for BALB/c mice, metastasizes to lymph nodes draining subcutaneous inoculation sites, and also to the lungs. T cell-mediated immunity was detected in Winn assays using spleens from excision immunized mice. T cell-mediated anti-tumour immunity was also detected in spleens from mice with small tumours but disappeared as the tumour burden increased. Protective immune spleen cell activity in the Winn assay was inhibited by prior addition of spleen cells from mice with large tumours, causing increased tumour incidence. Splenic metastases occasionally occurred in the MC-2 model, but were not demonstrable by bioassay in any of the experiments detecting splenic suppressor cell activity. In vivo protective activity was restored to advanced-stage tumour-bearer spleens by whole-body ionizing irradiation (0.5 and 2.5 Gy) of donor mice 15 h before sampling. Spleen cells from mice with small tumours remained protective after 1.5, 2.5 and 4.0 Gy of irradiation in vivo. These results are consistent with the properties of radiosensitive suppressor T cells. In contrast to reports in other tumour models, suppressor cells were not detected until late in the course of MC-2 development. This is surprising in view of the aggressively metastatic nature of MC-2. It is postulated that modulation of the anti-tumour immune response by the suppressor cells is associated with metastasis in this tumour model. The late appearance of both suppressor cells and metastatic cells in the spleen may reflect similar processes occurring earlier in regional lymph nodes.
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PMID:In vivo detection and partial characterization of effector and suppressor cell populations in spleens of mice with large metastatic fibrosarcomas. 315 16

The antigenic profile of C-26 and C-51 BALB/c colonic adenocarcinomas was examined by in vivo and in vitro assays. Mice immunized with irradiated C-26 or C-51 tumor cells from freshly excised tumor nodules or from in vitro-growing cell lines were able to reject a challenge of both tumors. Spleen lymphocytes of immune but not of normal mice were effective in cross-inhibiting tumor growth in vivo in a Winn assay. Tissue-associated antigens common to C-26 and C-51 and to their metastases but not to other syngeneic neoplasms were detected in vitro by cytotoxic T lymphocytes obtained after 5 days of a secondary culture of immune lymphocytes and irradiated tumor cells. Activated lymphocytes were obtained by exposure of spleen cells to interleukin 2 or by allostimulation. Such lymphocytes, although cytotoxic in vitro on C-26 and C-51 carcinomas, were unable to significantly reduce in vivo tumor growth in the Winn assay.
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PMID:Growth inhibition of murine colonic adenocarcinoma by tumor immune but not by IL-2-activated or alloactivated lymphocytes. 349 73

We have examined whether pertussis toxin, an agent known to inhibit entry of normal lymphocytes into tissues, affects invasion and metastasis formation by malignant lymphoma and T-cell hybridoma cells. The toxin reduced invasion in vitro in hepatocyte cultures to 20% of control values. Inhibition was maximal after pretreatment for 2 h with approximately 100 ng/ml. The effect of pretreatment with 1 to 5 micrograms toxin/ml for 4 h persisted for at least 5 days, despite a more than 100-fold increase in cell number. The proliferation rate was not affected. Liver metastasis formation after tail vein injection of TAM2D2 T-cell hybridoma cells in syngeneic AKR mice, measured as liver weight, was reduced to 10 to 25% of controls after pretreatment of the cells for 4 h with 1 microgram pertussis toxin/ml. Metastasis to kidneys, ovaries, and lymph nodes was not, or less evidently, affected. With MB6A lymphosarcoma cells no effect was seen after treatment with 1 microgram/ml, but a significant reduction of the liver tumor burden to approximately 50% of controls was achieved by treatment with at least 5 micrograms toxin/ml. Spleen metastasis by MB6A cells was not affected. These results provide evidence for a similarity in invasion mechanisms of normal and malignant lymphoid cells, and they suggest that invasiveness is an important factor in the formation of lymphoma metastases, particularly in the liver.
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PMID:Inhibition of lymphoma invasion and liver metastasis formation by pertussis toxin. 365 46

Spleen cells from rats bearing syngeneic metastatic 13762NF mammary adenocarcinoma clone MTLn3 tumors were fused with the rat myeloma Y3 Ag1.2.3 to generate a panel of monoclonal antibodies (MAbs). The MAbs could be divided into three groups: those cross-reactive with all 13762NF cells; those reactive with cloned MTLn3 and MTC cells; and those predominantly reactive with the highly metastatic MTLn3 cells. One of these MAbs, MT10:21 (an immunoglobulin G2a), binds predominantly to highly metastatic MTLn3 cells and has a high tumor-cell affinity as determined by its saturation kinetics. MAb MT10:21 has a 6-h half-life on the MTLn3 cell surface and a 24-h half-life in the blood of syngeneic rats. Immunoblotting experiments using lysates from the cloned 13762NF sublines revealed that MAb MT10:21 binds to several proteins having relative molecular weights of 72,000, 73,000, and 120,000. Using an immunohistochemical procedure with frozen tissue sections, MAb MT10:21 shows little reactivity with normal rat mammary tissue, irrespective of the stage of the estrous cycle, and it failed to react with a number of other normal fetal and adult tissues. Furthermore, MAb MT10:21 is heterogeneous in its reactivity to cloned sublines of the 13762NF mammary adenocarcinoma, on both tissue cultured cells and tissue sections prepared from tumors growing in situ in the mammary fat pads of syngeneic rats. MAb MT10:21 reacted with certain human breast cancer cell lines and with a subpopulation of metastatic human breast cancer cells in frozen tissue sections from biopsies and autopsies. Metastases from breast cancers reacted more intensely than the primary tumors from which they were derived.
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PMID:Monoclonal antibodies against cell-surface antigens of the metastatic rat 13762NF mammary adenocarcinoma and their cross-reactivity with human breast carcinomas. 377 54


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