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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the effect of hepatectomy on the growth of liver tumor, Shionogi Carcinoma 42, a mammary tumor, was transplanted into the liver of mice which had undergone 40% hepatectomy. The liver tumor and the number of pulmonary metastases in hepatectomized mice were significantly larger than those in nonhepatectomized mice. Responses to lectins and IL-2, subpopulations, and cytotoxicity to YAC-1 and P815 cells of splenocytes were assessed to evaluate immunological status. At the initial phase after hepatectomy and tumor transplantation into the remaining liver, NK activity transiently increased, and function of B and T cells, especially of helper T cells, decreased, while B-cell function recovered beyond normal levels in a later phase. These results suggest that liver may play an important immunological role and that the immunological modification after hepatectomy may be responsible for the accelerated growth of liver tumor. Accordingly, some adjuvant immunotherapy may be recommended for the prevention of recurrence after hepatectomy for liver tumor.
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PMID:Hepatectomy accelerates the growth of transplanted liver tumor in mice. 160 May 23

A new model for the generation of specific antitumor cytotoxic T-lymphocytes (CTL) was proposed. In contrast to other models, it allows to generate effector CTL without immunization in vitro. C57BL/10 mice or/and C57BL/6 mice were immunized by injection with gamma-irradiated syngeneic tumor cells into the footpads. For estimation of cytotoxic activity, chromium-51 release assay was used. It has been shown that effector CTL were absent in the lymph nodes in 1-fold as well as 2-fold immunization. Cytotoxic cells have not been found in 1-fold immunization even after maturation of the lymphocytes in monoculture. Specific CTL were detected only after secondary immunization and subsequent cultivation in vitro. Effector cells had Thy1.2+, Lyt2+, L3T4- phenotypes. Presence in vitro of exogenous IL-2 was needed for the generation of CTL against MX-11 sarcoma but not against EL4 lymphoma. We suggest that the release of IL-2 from lymphomas cells could stimulate generation of the effector cells through activation of the endogenous production of IL-2, or due to some other factors.
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PMID:[Formation of specific antitumor cytotoxic T-lymphocytes in monoculture]. 161 Oct 71

As reported earlier, the IL-2 induced lymphokine activated killer (LAK) activity is significantly up-regulated in the presence of cisplatin/FK-565. Based on these observations, we have investigated whether calcium is involved in the generation of LAK activity by IL-2 alone or along with CP/FK-565. We have shown that treatment of PBMC with IL-2 for four days caused an increase in intracellular free calcium and in ATP levels, which were further significantly enhanced when LAK cells were generated in the presence of CP/FK-565. Depletion of calcium resulted in decreased cytotoxic activity. Addition of tumor cells to LAK cells, generated in the presence of IL-2 alone or along with CP/FK-565 caused an instant rise in intracellular free calcium which was significantly decreased when an increase in intracellular free calcium was observed in calcium-free, EGTA-containing buffer. These data suggest that calcium is required for the activation and manifestation of lytic activity by LAK cells. Further, we observed that the increase in intracellular free calcium is not associated with the blastogenic response of peripheral blood mononuclear cells in response to treatment of IL-2 alone or together with CP/FK-565.
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PMID:Up-regulation of IL-2 induced lymphokine activated killer cell activity by cisplatin and FK-565: involvement of calcium ion. 161 37

Polyethylene glycol-modified recombinant human interleukin-2 (PEG-IL-2) represents a cytokine with prolonged circulatory half-life and increased antitumor activity as compared to recombinant interleukin-2 (rIL-2) after systemic administration. We studied whether PEG-IL-2 would also be advantageous in locoregional immunotherapy using a syngeneic tumor model. Intradermal inoculation of line-10 tumor cells into the flanks of strain-2 guinea-pigs results in a fast-growing tumor and regional lymph-node metastases. Treatment schedules were started on day 7 after inoculation in animals with established tumors. First, groups of 5-6 animals were treated with repeated intratumoral and perilymphatic rIL-2 or PEG-IL-2 injections. PEG-IL-2 caused significant growth inhibition of both the primary tumor and the regional lymph-node metastases at lower doses and with less frequent administration than rIL-2. The best schedule for PEG-IL-2 was 3 injections a week for 5 weeks, resulting in cure of 4/17 and 5/5 (p less than 0.01) animals at the 2 most efficient dose levels tested. Subsequent experiments indicated that the intratumoral and not the perilymphatic injection route was essential for the obtained antitumor effect. Furthermore, 12/12 animals cured after PEG-IL-2 treatment rejected a rechallenge with line-10 tumor cells, whereas no cures were seen after rIL-2 injections. PEG-IL-2 therefore appears to be a valuable substance for intratumoral immunotherapy.
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PMID:Polyethylene-glycol-modified interleukin-2 is superior to interleukin-2 in locoregional immunotherapy of established guinea-pig tumors. 161 87

The effects of Krestin (PSK) on the generation of lymphokine-activated killer (LAK) cells were examined in tumor-bearing mice. BALB/c mice were inoculated subcutaneously with methylcholanthrene-induced fibrosarcoma (Meth A) cells, and PSK was administered intraperitoneally every other day. The reduced LAK activity in tumor-bearing mice was restored by the administration of PSK. Since involvement of the humoral immunosuppressive factor in the impairment of LAK activity has been suggested, the effect of PSK on the impaired LAK activity in the presence of an immunosuppressive factor isolated from the ascites of X5563 (plasmacytoma)-inoculated mice was examined. The activity reduced by the immunosuppressive factor in an in vitro induction of LAK was restored by incubation with PSK. The antimetastatic effect of IL-2 was also augmented by its combined use with PSK. The data provide a rational basis for using PSK in combination with recombinant IL-2 in cancer immunotherapy.
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PMID:Effect of Krestin (PSK) on the induction of IL-2 activated killer cells. 161 82

Expansion of tumor infiltrating lymphocytes (TIL) in vitro is hampered by several factors, including a limited amount of lymphocytes obtained from different tumors, unknown target antigens and limited supply of antigen-presenting cells (APC) which are generally believed to be essential in the classical way of T cell stimulation and expansion. In approaching these difficulties, we have recently used surface-oxidized allogeneic PBL to stimulate the TIL periodically in the presence of a low dose of rIL-2 (200 IU/ml). TIL derived from 22 (out of 23) tumor specimens could be expanded with 20 -10(7) fold increases over 6-16 weeks to a sufficient amount of 10(9) -10(11) cells for adoptive immunotherapy. In contrast, only 2-100 fold increase were observed in six tumor specimens (out of 23) when 200 IU/ml rIL-2 was used only. The phenotypes, autologous tumor reactivity and cytolytic capability of TIL propagated with surface-oxidized stimulators were similar to those expanded in the presence of IL-2 alone. These data suggest that expanding TIL with surface-modified stimulator cells could be a useful alternative method to obtain a large amount of tumor specific cytolytic T cells for clinical immunotherapeutic use, irrespective of tumor-antigen stimulation and MHC restriction.
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PMID:Large scale expansion of human tumor infiltrating lymphocytes with surface-modified stimulator cells for adoptive immunotherapy. 162 31

The role of uncultured melanoma cells in the proliferation of autologous tumor-specific cytotoxic T lymphocytes (CTLs) was investigated. Uncultured autologous tumor cells by themselves induced modest, but significant, proliferation in 10 of 13 (77%) CTL clones and in only two of nine non-CTL clones. Uncultured allogenic melanoma cells mostly failed to induce CTL proliferation. Autologous tumor-induced CTL proliferation declined with increasing age of the culture. It did not correlate with IL-2 receptor-alpha expression or was not inhibited by addition of anti-IL-2 antibody to the culture. It was inhibited by pretreatment of tumor cells with anti-MHC class II, but not -MHC class I mAb. IL-2 alone was sufficient for the potent proliferation of five of nine CTL clones. In all these five CTL clones, autologous tumor cells suppressed IL-2-induced proliferation. The remaining four CTL clones, however, required both uncultured autologous melanoma cells and IL-2 for the proliferation. IL-4 or IL-6, in particular IL-6, facilitated IL-2-induced CTL proliferation, but not their cytotoxicity. In summary, uncultured melanoma cells by themselves induced modest levels of CTL proliferation in the context of MHC class II antigens, whereas they suppressed IL-2-induced CTL proliferation in more than half of the clones.
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PMID:Role of uncultured human melanoma cells in the proliferation of autologous tumor-specific cytotoxic T lymphocytes. 162 65

To try to understand the functional significance of human melanoma-infiltrating lymphocytes (TIL), a clonal analysis of the specificity, T cell receptor (TcR) diversity and activation requirements of these lymphocytes isolated from four different tumors was carried out. Supporting the presence of in vivo primed tumor-specific T lymphocytes in these four tumors, a high frequency of the Cd8+ and CD4+ clones, obtained from the TIL cultured for a few days with recombinant interleukin (rIL)-2 and autologous tumor cells, exhibited a restricted lysis or proliferation in response to the autologous tumor cell line. In contrast, no tumor-specific clone was obtained from freshly extracted TIL, suggesting that the frequency of tumor-specific effectors remained low in these tumors. Only the CD8+ clones lysed the autologous tumor cells and their activity was major histocompatibility complex MHC class I restricted. Significant expansion of CD4+ and CD8+ tumor-specific clones required regular restimulation by autologous melanoma cells but also the addition of exogenous IL-2 and of Epstein-Barr virus-transformed B feeder cells. Five different tumor-specific clones, three CD8+ and two CD4+ clones were identified in a single tumor on the basis of their TcR gene configuration. Together, these data suggest that a spontaneous and diverse immune response, mediated by tumor-specific CD4+ as well as CD8+ T lymphocytes, arises in most MHC-bearing human melanomas but that antigen-MHC complex presentation by tumor cells does not, at least in vitro, allow a significant proliferation of these lymphocytes.
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PMID:Specificity, T cell receptor diversity and activation requirements of CD4+ and CD8+ clones derived from human melanoma-infiltrating lymphocytes. 162 24

Expression of the human IL-6 gene in EBV-immortalized normal human B lymphocytes following retroviral-mediated transduction rendered these cells highly tumorigenic in athymic mice. The tumors were lymphomas composed of the originally inoculated human lymphoblastoid cells. Co-injection of IL-6 expressing EBV-immortalized cells with IL-6 nonexpressing control cells resulted in increased tumorigenicity of the IL-6 nonexpressing cells. The lymphoblastoid cells expressing IL-6 were indistinguishable from parental cell lines in morphology and in a variety of cell surface characteristics, and did not exhibit growth advantage over parental cell lines in vitro, such that increased tumorigenicity is unlikely to depend upon a direct oncogenic effect of IL-6 on the B cells. Rather, at high concentrations, IL-6 markedly inhibits human lymphoblastoid cell killing by IL-2-activated murine splenocytes in vitro, suggesting that IL-6-related tumorigenicity might depend upon IL-6 inhibiting cytotoxicity at the tumor site. Thus, production of IL-6 by tumor cells that results in natural killer cell dysfunctions illustrates a novel mechanism of tumor cell escape from immune surveillance.
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PMID:Impairment of natural killer functions by interleukin 6 increases lymphoblastoid cell tumorigenicity in athymic mice. 164 16

We have studied growth, function, and phenotype of purified NK and T cells in long-term cultures and compared these parameters to those of conventionally prepared interleukin-2-activated lymphocytes with killer cell activity (LAK). Enrichment of NK and T cells was achieved by Percoll density gradient. Growth was analyzed by cell counts and [3H]TdR uptake. Cytotoxicity and tumor-binding efficacy were assessed in a 3-h 51Cr and single cell agarose assay, respectively, against K-562, Daudi, human ovarian cell line Ovcar-3, and fresh leukemic blasts. We found that long-term proliferation and lytic activity were highest in NK-enriched and lowest in T-enriched cultures. Conventional LAK cultures generated medium cytotoxicity levels. Lytic activity declined within 3 weeks in cultures not enriched for NK cells, while NK-enriched cultures showed high levels of cytotoxicity up to 6 weeks. No change was found in binding activity within 3 weeks with the exception of T cell-enriched fraction. A number of changes in the phenotypic patterns was observed in IL-2 cultures; the CD56+/CD3-/+ and CD56+/CD8+ subset increased in most cultures, whereas the CD56-/CD3+ subset decreased over time. The highly enriched NK cell culture maintained its NK cell phenotype over 5-6 weeks. We also delineated the most cytotoxic lymphocyte subset in long-term IL-2 cultures by complement dependent cytotoxic assays and fluorescence-activated cell sorting (FACS). Lytic activity in conventional LAK as well as in T and NK cell-enriched IL-2 cultures was mediated primarily by CD56+, CD16+, CD3- NK cells. The clinical implication of these studies is discussed.
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PMID:Antitumor activity, growth, and phenotype of long-term IL-2 cultures of human NK and T lymphocytes. 165 70


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