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 leukocyte adherence inhibition (LAI) microassay detects tumor-associated antigen(s). Extracts of colon carcinoma (MCA-38 and B16 melanoma tumors, both syngeneic to the C57BL/6J mice) are recognized only by peritoneal cells from mice bearing the corresponding tumor. To ascertain whether this in vitro antigenic recognition correlates with the ability of the host to recognize and reject a tumor in vivo, serial LAI microassays were performed synchronously with experiments designed to test the ability of mice bearing tumors to reject live secondary tumor challenges. Concomitant tumor immunity was present in the MCA-38 tumor-bearing mice on 3 occasions from 5 to 15 days from primary inoculation. In the B16 system, concomitant immunity was present on one occasion 10 days after primary inoculation. These results in turn were paralleled with the specific in vitro recognition of tumor antigens as detected by the LAI microassays. Loss of immunity in the "eclipse" phase of tumor development, as detected by concomitant tumor immunity, was paralleled by nonreactivity of the indicator cells in the LAI microassay.
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PMID:Correlations between the leukocyte adherence inhibition microassay and in vivo tests of transplantation resistance. 36 84

Syngeneic murine colon adenocarcinoma (MCA-38) cells were transplanted in the submucosa of distal colon, proximal colon, cecum, ileum, jejunum, and duodenum of male C57BL/6 mice, with local lymphoid follicles used as points of entry. The tumor grew best at the cecum and led to liver and mesenteric lymph node metastases in 8 and 9 weeks, respectively, after transplantation. Histologically, a local inflammatory reaction involving polymorphonuclear leukocytes was observed within 48-72 hours following transplantation; after this time, the microscopic tumor foci began to grow progressively. Mononuclear lymphoid cells of the gut-associated lymphoid tissue did not infiltrate the progressively growing tumor; however, polymorphonuclear leukocytes were constantly observed at the tumor periphery in the lamina propria. The studies indicated that orthotopic transplantation as a model system can provide a means of examining the role of the local immune response as a focus of host resistance and as a factor in metastatic tumor spread. The findings also suggested the usefulness of this model in immunotherapeutic and chemotherapeutic studies of secondary hepatic disease.
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PMID:Murine colon adenocarcinoma: syngeneic orthotopic transplantation and subsequent hepatic metastases. 90 10

Challenge of C57(nu/nu) mice with an MCA-induced sarcoma, MCG101, induced in C57BL/6J mice, disclosed a higher resistence subcutaneously and intravenously than in syngenic C57/(+/+) mice. Transfer of 5 X 10(7) thymus cells to the nude mice brought their resistance to subcutaneously injected tumour cells back to the level of the C57/(+/+) mice, but only with the highest tumour cell doses tested, i.e. 5 X 10(4) and 10(5) cells. Against intravenously injected tumour cells a similar effect by the thymus cells was only suggested. Spontaneous metastases from the same tumour transplanted to the tail did occur in the nude mice and were possibly facilitated by specifically sensitized spleen cells. The results indicate that the resistance to subcutaneously injected tumour cells in nude mice may well be dependent on their incapability to develop thymus-dependent immuno-responses and that spontaneous metastases can be facilitated by a weak immuno-response.
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PMID:Transplantability and metastasibility of an MCA-induced sarcoma in nude mice. Influence of transfer of thymus cells and adoptive immunity. 92 Jan 88

A previous observation that increased spontaneous metastasis formation from the highly antigenic MCA-induced sarcoma MCG101 occurred in immunosuppressed C57BL/6J mice prompted the present study to establish whether or not tumours capable of inducing only weak transplantation resistance would behave similarly. One MCA-induced sarcoma, MCG12, one epidermoid carcinoma, EpCa1 in CBA mice and a spontaneous mammary carcinoma, MaCa1 in C3H mice, were transplanted into adult thymectomized and/or sub-lethally irradiated mice at different intervals after irradiation. The effects of the treatments on the immunoreactivity were monitored in separate groups by determining the primary and secondary responses to SRBC and the survival of first set allogeneic skin grafts. The treatment resulted in a significantly increased incidence of mainly the lymph-node metastases with MCG12 and of only the lung metastases with EpCa1. No increase in metastases was noted with MaCa1. Thymectomy potentiated the increase in metastases from MCG12 in irradiated mice but unexpectedly so only for a limited time after irradiation. Local growth of MCG12 and MaCa1 at the transplantation site was more rapid in females than in males. The changes in tumour growth and spread induced by the treatments varied with tumour-host system, sex and time of transplantation after irradiation and did not conform well with any of the tested parameters of immunoreactivity. There was no close parallel between the effects of the treatments on growth and spread of the tumours.
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PMID:Tumour metastasis in mice with reduced immune reactivity. III. Studies with three weakly antigenic tumours in thymectomized and/or sub-lethally irradiated mice. 117 1

When lymphocytes from the lymph nodes draining the site of a progressively growing MCA-105 sarcoma are stimulated in vitro with autologous tumor and low-dose interleukin-2 (IL-2), they will grow and develop the ability to lyse autologous tumor cells in vitro; these lymphocytes can also eradicate tumor metastases in vivo. Phorbol esters and calcium ionophores activate signal transduction pathways in T cells and mimic the events triggered by antigen binding. We therefore sought to determine whether large numbers of MCA-105 tumor-specific, therapeutically active T cells could be obtained from MCA-105 draining lymph nodes (DLNs) following a brief exposure to phorbol dibutyrate (PDBu) and ionomycin (Io). DLN cells primarily stimulated with autologous tumor, followed by a secondary stimulation with PDBu-Io and cultured in 20 U/ml IL-2, demonstrated marked expansion of cell numbers during 3 weeks in culture, had moderate cytolytic activity [37% at effector:target ratio (E:T) = 80:1], and were all CD8+ T cells. In contrast, DLN cells stimulated primarily with PDBu-Io and cultured in 20 U/ml IL-2 demonstrated at least 8-10-fold greater growth than antigen-stimulated DLN cells during 3 weeks, were moderately cytolytic (31% at E:T = 80:1), and were a mixed population of CD8+ and CD4+ T lymphocytes. DLN cells that were expanded by either protocol, like cells stimulated repeatedly in vitro with tumor cells, could eliminate MCA-105 pulmonary metastases when given with IL-2 in an adoptive immunotherapy model. DLN cells stimulated primarily with PDBu-Io completely eradicated MCA-105 metastases but had no in vivo antitumor activity against the syngeneic B16 melanoma or MCA-203 sarcoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of CD8+ murine T cells from tumor-draining lymph nodes by phorbol dibutyrate plus calcium ionophore. 138 51

We have previously described an in vitro sensitization (IVS) procedure which enabled the generation of therapeutic T cells from tumor-bearing mice for adoptive immunotherapy. The procedure involved culture of tumor-draining lymph node (TDLN) cells with irradiated tumor in the presence of interleukin-2 (IL-2). The availability of many recombinant cytokines affords an opportunity to examine their effects on the immune response to tumor. In this study, we investigated the effect of tumor necrosis factor-alpha (TNF alpha) on the generation and function of IVS cells utilized in adoptive immunotherapy of the murine MCA 106 sarcoma. TNF alpha administered iv at nontherapeutic doses was found to enhance the antitumor efficacy mediated by IVS cells plus IL-2 in the treatment of pulmonary metastases. In contrast, TNF alpha administration to mice bearing progressive footpad tumors had inhibitory effects on the sensitization of tumor-reactive cells in TDLN since IVS cells generated from these animals displayed a diminished antitumor effect. This effect appeared to be due to a reduced number of tumor-reactive lymphoid cells in the TDLN since TNF alpha added to IVS cultures did not alter the antitumor efficacy of the resultant IVS effector cells. These findings indicate the divergent effects of TNF alpha on the immune response to tumor and adoptive immunotherapy with IVS cells.
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PMID:Divergent effects of TNF alpha in the adoptive immunotherapy of a murine sarcoma. 140 3

This investigation aimed to develop a biologically relevant murine model of colorectal liver metastases and determine if Kupffer cells (KC) and hepatic natural killer cells (hNKC) regulate tumor growth. The model involves the injection of murine colon adenocarcinoma 26 (MCA 26) tumor cells into the portal vein of female-specific pathogen-free BALB/c mice. Metastases developed in all animals, and the growth was limited entirely to the liver. To determine if KC and hNKC control the development of liver metastases, the in vivo function of these hepatic effector cells was modulated. Tumor growth was quantitated by the uptake of 125I into tumor DNA. Stimulation of the KC and hNKC produced a significant (P less than 0.01) dose-dependent decrease in 125I uptake in the liver in both treatment groups, which was associated with a significant improvement in survival (P less than 0.05). The in vivo cytotoxic function of the liver was inhibited with an intravenous injection of gadolinium chloride (for KC) or asialo GM1 antiserum (for hNKC). Inhibition of KC and hNKC cytotoxic function led to a significant (P less than 0.01) increase in 125I uptake in the liver and a significant decrease in survival (P less than 0.05).
Clin Exp Metastasis 1992 Sep
PMID:Murine Kupffer cells and hepatic natural killer cells regulate tumor growth in a quantitative model of colorectal liver metastases. 150 22

Adoptive immunotherapy in humans may be limited by the lack of autologous tumor cells to activate and expand tumor-specific T cells. Pharmacologic manipulation of protein kinase C (PKC) and intracellular calcium may substitute for tumor antigen and stimulate T cells for adoptive immunotherapy. In the present study, we evaluated the ability of the PKC activator Bryostatin 1 (B) plus the calcium ionophore ionomycin (I) to activate lymphocytes obtained from popliteal lymph nodes (DLN) draining an MCA-105 footpad tumor. The adoptive transfer of B/I-stimulated DLN cells eradicated MCA-105 pulmonary metastases. These lymphocytes do not require concomitant IL-2 administration to mediate regression of lung metastases. Three days after intrasplenic injection of tumor cells and splenectomy, mice were given iv injections of B/I-stimulated DLN cells. Adoptive immunotherapy with these cells induced regression of established liver metastases. In an intradermal tumor model, the adoptive transfer of B/I-stimulated MCA-105 DLN cells cured mice of MCA-105 intradermal (id) tumors, but did not induce regression of MCA-206 tumors. Mice cured of MCA-105 id tumors were protected against MCA-105, but not MCA-203, tumor challenge in the footpad 7 weeks after adoptive immunotherapy.
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PMID:Bryostatin 1-activated T cells can traffic and mediate tumor regression. 152 28

After surgery and radiotherapy circulating serum levels of the tumour markers MCA and Ca 15-3 were evaluated in 226 clinically disease-free breast cancer patients. 15 of them presented with local recurrences and/or distant metastases after a follow-up period of twelve months. Six patients belonged to the group of 180 with both markers negative, two belonged to the 32 patients with only one marker positive, and seven to the group of 14 with both markers positive. After twelve months the probability of disease-free survival (calculated by the method of Kaplan-Meier) is 96% in patients with negative tumour markers and only 51.4% in patients with both markers positive (p less than 0.001). After 16 months these values are 96% versus 25.7% with the same statistical significance. The value of tumour marker examinations in the regular follow-up of patients with breast cancer lies in the early detection of tumour activity and therefore in a better chance of response to subsequent treatment. The diagnostic sensitivity of MCA was 75.5%, and for Ca 15-3 70.24%.
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PMID:[MCA and CA 15-3 in the follow-up of patients with breast cancer]. 154 44

The aim of the present study has been to assess the therapeutic efficacy of various cytokines, singly or in combination, with and without chemotherapy (cyclophosphamide, Cy), in mice carrying advanced, weakly immunogenic tumors (MCA-105 sarcoma, M109 carcinoma). Treatment of animals with i.p. growths or experimental pulmonary metastases began 8-18 days after i.p. or i.v. tumor cell inoculation respectively. None of the cytokines tested [interleukin-2 (IL-2), interferon alpha (IFN alpha), tumor necrosis factor alpha (TNF alpha) and macrophage-colony-stimulating factor (M-CSF)] nor Cy had by itself a significant curative effect. A synergistic therapeutic effect was obtained with IL-2 or IFN alpha (but not with TNF alpha or M-CSF) in combination with Cy. The most efficacious regimen (65%-90% cure of mice carrying i.p. tumors) was the combination of Cy+IL-2+IFN alpha. Preliminary experiments suggested that sequential administration of these cytokines might be more beneficial than concurrent administration. Following successful immunotherapy, long-term (3-6 months) survivors showed a tumor-specific resistance to a second tumor challenge and their spleen contained an increased number of specific antitumor cytotoxic T lymphocyte precursors (5- to 20-fold, compared to control mice). In vitro and in vivo cell-depletion experiments using monoclonal antibodies revealed that T cells (primarily CD8), but not NK cells, are crucial for the therapeutic effects. This study indicates that a potent specific antitumor T cell immunity can be elicited against advanced weakly immunogenic tumors by combining chemotherapy (Cy) with IL-2 and IFN alpha.
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PMID:Chemo-immunotherapy of murine solid tumors: enhanced therapeutic effects by interleukin-2 combined with interferon alpha and the role of specific T cells. 161 25


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