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)

Peripheral blood lymphocytes obtained from patients by leukapheresis were cultured in RPMI 1640 containing human plasma and interleukin 2. The morphology, phenotypes and cytotoxicity of induced LAK cells were studied. Lymphoblastoid cells mainly proliferated were OKIa1+ cells and were thought to be LAK cells. Maximal cytotoxicity was obtained after two weeks of incubation. IL-2 enhanced the cytotoxicity of LAK cells. Autologous LAK cells induced by two weeks of incubation were injected into patients. One case of pulmonary metastases of breast cancer showed reduction and two lesions showed partial regression. Also, no new lesions appeared in the lungs of a patient with alveolar soft-part sarcoma.
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PMID:[Adoptive immunotherapy of malignant diseases with LAK cells]. 349 32

Effectiveness of IL-2 and LAK cells induced by IL-2 on malignant diseases was discussed. IL-2 alone administered systemically showed a poor effect, and combination of IL-2 are necessary for LAK cells to kill the target malignant cells. Adoptive immunotherapy using IL-2 and LAK cells should be applied for pulmonary and hepatic metastases. Postoperative adjuvant therapy and combination with chemotherapy will become important in the future.
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PMID:[Interleukin 2]. 349 39

The in vivo anti-tumor activity of 2 recombinant cytokines, interleukin-2 (rIL-2) and human hybrid interferon alpha (rHuIFN-alpha A/D), were tested using the murine reticulum cell sarcoma M5076. Experimental hepatic metastases, following i.v. injection of tumor cells, and tumor growth and spontaneous metastases, following s.c. injection of tumor cells, were inhibited to a greater extent in mice treated with a combination of these cytokines than in animals treated with either one alone. When used in conjunction with surgical removal of the s.c. tumor, treatment of mice with both cytokines significantly prolonged survival of tumor-bearing animals. Injection of normal mice with a combination of cytokines, but not with either cytokine alone, resulted in a marked increase in cytotoxic activity of hepatic effector cells. The effector cells in these mice appeared to be NK cells since this enhanced cytotoxicity was markedly reduced in animals treated in vivo with anti-asialo GM1 or in NK-deficient beige mice. Furthermore, no in vivo efficacy was observed in M5076-bearing beige mice treated with these cytokines. Thus, injection of mice with rIL-2 and rHuIFN-alpha A/D results in the induction of an NK-cell-like population in the liver with enhanced cytotoxic activity that correlates with the observed anti-tumor activity in vivo in this murine model. These results suggest that combinations of cytokines, in particular IFN-alpha and IL-2, can be effectively used in combination for the treatment of tumors and/or metastases.
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PMID:In vivo anti-tumor activity of combinations of interferon alpha and interleukin-2 in a murine model. Correlation of efficacy with the induction of cytotoxic cells resembling natural killer cells. 349 83

Cytotoxic activity of lymphocytes cultured in IL-2 against autologous primary lung cancer cells was studied in relation to curativity, prognosis and relapse rate. A total of 51 patients, 44 males and 7 females, consisting of those with adenocarcinoma (n = 27), squamous cell carcinoma (n = 19), large cell carcinoma (n = 2), small cell carcinoma (n = 1), lung sarcoma (n = 1), and carcinoid (n = 1), were evaluated. Pathological stages of the patients were stage I (n = 16), stage II (n = 1), stage III (n = 28), and stage IV (n = 6). Thirteen patients (25.5%) underwent curative surgery, 23 patients (45.1%) received relative curative surgery and 15 patients (29.4%) received non-curative surgery. The mean value of cytotoxic activity in the patients who received curative surgery was 34.7 +/- 15.3%, relative curative surgery 26.5 +/- 18.9%, and non-curative surgery 42.8 +/- 22.3%. Among the patients who underwent curative and relative curative surgery, 23 patients survived more than 2 years and 13 patients died of cancer recurrence. Mean value of cytotoxic activity in the former (36.7 +/- 15.9%) was significantly (p less than 0.01) higher than that in the latter (17.1 +/- 14.7%). Positive rate (percentage of patients whose CA exceeded 15%) of the former (86.9%) was also higher than that of the latter (46.1%). Comparison between the survival curves of the positive cases (CA 15.0%) and negative cases (CA less than 15.0%) revealed a significantly better prognosis for the former (generalized Wilcoxon test: W/square root VarW = 2.198). The mean cytotoxic activity in the cases of local recurrence (25.7 +/- 16.6%, n = 7) was higher (p less than 0.10) than that in the cases with distant metastases (9.3 +/- 6.3%).
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PMID:[Cytotoxic activity of autologous lymphocytes against lung cancer cells; correlation of prognosis and recurrence pattern]. 349 20

The capacity of inbred W/Fu rats bearing syngeneic colon carcinomas to generate interleukin(s) (IL) was studied during primary tumor growth, after tumor resection, and during postresection immunotherapy. During local tumor growth, there was a significant decrease in the capacity of the host's adherent mononuclear cells to generate IL-1 and of peripheral blood mononuclear cells to generate IL-2 (16.6 and 23%, respectively, when compared to control animals; P less than .01). The presence of regional metastases or large primary tumor burden resulted in a further sharp fall in IL generation (0.9 and 10% for IL-1 and IL-2, respectively, when compared to control animals; P less than .01). With the use of three different doses of tumor inoculum, inhibition of IL generation was shown to occur when tumors were barely palpable. Decrease in IL correlated with tumor growth and not with the initial number of tumor cells injected. Tumor resection resulted in a rise in IL-2 generation from 36 to 64% of control animals' levels. Postresection immunotherapy with the use of an active specific immunization protocol successfully modulated IL-2 production to normal in animals protected from tumor recurrence. Animals that developed recurrent tumors despite immunization exhibited a continued inability to generate IL (mean values of IL-2 production compared to controls: 184% in animals free of recurrence after immunotherapy, 1% in animals developing recurrent tumors after immunotherapy; P less than .01). These results suggested that alterations in IL generation may lead to immune unresponsiveness during tumor growth. Active specific immunotherapy protecting animals from recurrence after primary tumor resection may be predicated on the successful modulation of IL level generation by host immunocytes.
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PMID:Interleukin generation in experimental colon cancer of rats: effects of tumor growth and tumor therapy. 387 59

Evidence for heterogeneity of several biological features of human malignant melanoma (Me) like morphology, cytogenetics, oncogenes activation, antigenic expression, metastatizing capacity and procoagulant activity are briefly reviewed in an attempt to distinguish findings related to primary vs. metastatic lesions. In our own studies monoclonal antibodies were used to study expression of MHC class I, class II products and of Me-associated antigens (MAA) on primary and metastatic Me cells. High expression of class I antigens was found in a high percentage of both primary and metastatic tumors, whereas DR and MAA showed a significant variation (from 3 to 90% of cells) in expression both in primary and in metastatic Me. When autologous cell-mediated immune responses were evaluated, it was found that Me cells from primary tumors but not those from lymph node metastases were able to stimulate autologous lymphocytes to proliferate and become cytotoxic for autologous Me. Clonal analysis of cytotoxic lymphocytes was then carried out in order to see whether the lack of lymphocytes reactivity to metastatic cells was due to the absence or to a low frequency of cytotoxic cells in the unstimulated PBL. CTL clones cytotoxic for autologous Me (Auto-Me) cells were indeed isolated. Three classes of CTL clones were identified: 1) one which is cytotoxic for Auto-Me; 2) a second one which lyse Auto-Me and allogeneic Me; and 3) a third one which is cytotoxic for Auto-Me and allogeneic normal and neoplastic cells. Metastatic Me cells, however, had the ability to suppress the stimulation of autologous PBL by alloantigens or IL-2. This effect was dose-dependent and was not due to absorption of IL-2 by Me cells. Since it has been reported that Me cells express class II MHC antigens, we investigated whether there was any correlation between autologous immune responses and DR expression on Me cells. Autologous lymphocytes stimulation was found to occur only with DR+ Me cells from primary lesions, whereas metastatic cells, either DR+ or DR-, did not stimulate autologous PBL. Moreover, the suppressive effect of metastatic Me cells was associated with their expression of DR antigens. The modulation of DR antigens on Me cells by Interferon-gamma correlated positively with their suppressive capacity. Thus, it appears that primary Me can behave differently from the metastatic one in their interactions with the immune system of autologous host. These findings suggest that DR antigens on Me cells may have an important role in the regulation of autologous immune responses.
Cancer Metastasis Rev 1985
PMID:Autologous cellular immune response to primary and metastatic human melanomas and its regulation by DR antigens expressed on tumor cells. 388 84

Intravenous inoculation of the AKR mouse-strain-derived BW lymphoma into CBA recipients resulted in a case of liver metastasis; cells derived from this metastatic nodule were termed BW-Li cells. BW-Li cells, upon reinoculation, generated metastases in the spleen, liver, kidney and ovaries in 100% of CBA recipients. Furthermore, BW-Li cells, in contrast to BW cells, were found to infiltrate in vitro monolayers of hepatocytes, thus confirming their inherent invasive potential. Analysis of the alloantigenic phenotype of BW-Li cells revealed that such cells were Thy 1.1+, Thy 1.2+, Lyt 1.2+, Lyt 1.1-, Lyt 2- and H-2Dk+, as compared to BW cells which exhibited the membrane phenotype Thy 1.1+, Thy 1.2-, Lyt 1.2-, Lyt 1.1-, Lyt 2-, H-2Dk-. BW-Li cells also differed functionally from BW cells since these cells secreted IL-2 upon stimulation with Concanavalin A. BW tumor transplantation experiments were repeated in a semi-allogeneic F1 strain combination, i.e. (AKR X CBA)F1, and again a case of massive liver metastasis was observed. Cells derived from these liver metastases (termed BW-O-Li) manifested an invasive and metastatic potential similar to that of BW-Li cells. Furthermore, BW-O-Li cells secreted IL-2 upon stimulation with Con A and manifested the following alloantigenic phenotype: Thy 1.1+, Thy 1.2+, Lyt 1.2+, Lyt 1.1-, Lyt 2-, H-2Dk+ and H-2Kk+. These results indicate that BW-Li and BW-O-Li cells are functional T-cell hybrids which express T-cell markers derived from BW cells and Thy 1.2+ CBA host cells. The acquisition of host-derived T-cell properties may have led to the expression of metastatic and invasive capabilities. From these results we conclude that the acquisition of metastatic properties following somatic cell fusion with normal lymphoreticular cells may represent a mechanism for tumor progression in vivo.
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PMID:Generation of invasive and metastatic variants of a non-metastatic T-cell lymphoma by in vivo fusion with normal host cells. 633 39

This study delineates the temporal relationship between immune complex formation and tumor growth, and provides one possible explanation for host immunosuppression during tumor growth. The authors have studied serial circulating immune complex (CIC) levels and interleukin (IL) elaboration by peripheral blood cells (IL-1 production by adherent mononuclear cells [AMC]; and IL-2 generation by peripheral blood mononuclear cells [PBMC]) during the growth of syngeneic tumor isografts in an inbred rat model. Male Wistar/Furth (W/Fu) rats were injected, subcutaneously (SC) with 2 X 10(6) W163 ( a dimethylhydrazine [DMH]-induced colon adenocarcinoma) cells into their hind limbs. Serial CIC levels, (measured by the antigen nonspecific polyethylene glycol turbidity assay) and IL-1 and IL-2 production were measured before isografting and weekly thereafter. Progressive local tumor growth occurred for 3 weeks followed by regional lymph node metastases during the fourth week. During local tumor growth, there was a progressive rise in CIC levels (123% rise compared with baseline value; P less than 0.05) which correlated with a fall in both IL-1 and IL-2 generation (r = -0.768). At the time of regional metastasis, the mean CIC levels declined, and there was a further significant decrease in IL production (IL-1 = 0.9% and IL-2 = 10% of controls in tumor bearers). These results show that progressive tumor growth results in decreased IL production by host PBC, and suggest that CIC may be involved in regulating IL generation.
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PMID:Effects of tumor growth on interleukins and circulating immune complexes. Mechanisms of immune unresponsiveness. 660

We have studied the ability of immunized lymphoid cells expanded in IL-2 to mediate the cure of mice with localized and disseminated syngeneic lymphoma. Mice received 500 rad total-body irradiation before injection of tumor into the footpad. Mice were treated 5 d later when a palpable local tumor and disseminated metastases were present. Intravenous injection of in vivo immune lymphocytes cured 93% of all mice, significantly better than any control group (P less than 0.0005). Immune cells, secondarily sensitized to the FBL-3 tumor in vitro, also conferred significant survival benefit (P less than 0.005) when injected intravenously, curing 79% of the animals treated. When these in vitro sensitized cells were expanded in IL-2, 8-10-fold over 7 d, 93% of the animals thus treated were cured, (P less than 0.005). When these cells were grown for multiple generations in IL-2 they retained their ability to cure mice (56% cured, P less than 0.01). This is the first demonstration that intravenous injection of sensitized cells grown in long term culture in IL-2 is capable of curing mice of established local and disseminated syngeneic tumor.
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PMID:Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2. 698 Feb 54

Transfer of cytokine genes into tumor cells has proven a valuable approach for cancer treatment. In order to generate a more effective cancer vaccine, we transfected the human interleukin-6 (IL-6) gene into B16 melanoma cells. A B16 cell clone secreting the highest level of IL-6 was obtained by G418-resistant selection, limiting dilution and IL-6 assay. The IL-6-gene-transfected tumor cells exhibited in vitro growth inhibition, reduced tumorigenicity and decreased metastatic competence. After immunization with the inactivated IL-6-gene-transfected vaccine, the murine cytotoxic T lymphocyte activity, natural killer activity and lymphokine-activated killer activity increased markedly. After treatment with the vaccine, the tumor-bearing mice showed significant growth inhibition of subcutaneous tumor, reduction in pulmonary metastases and extension of survival time. The above therapeutic effect was better when low-dose IL-2 was administered simultaneously, although this dosage of IL-2 had no in vivo antitumor effect. These data demonstrated that IL-6-gene-transfected cancer vaccine has a potent antitumor effect via efficient induction of antitumor immunity, and a better therapeutic effect could be achieved when the vaccine is combined with low-dose IL-2 as adjuvant.
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PMID:Induction of antitumor immunity and treatment of preestablished tumor by interleukin-6-gene-transfected melanoma cells combined with low-dose interleukin-2. 749 43


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