Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro culture of murine spleen cells with Corynebacterium parvum (C. parvum) was found to induce lymphokine-activated killer (LAK)-like cells capable of killing both natural killer (NK)-sensitive and NK-resistant tumor cells as well as syngeneic macrophages (M phi). The induction of LAK-like activity by C. parvum was significantly inhibited by anti-interleukin-2 (IL-2) or anti-interferon (IFN) alpha, beta antibody (Ab), and it was further inhibited by the combination of two Abs, suggesting that the generation of killer cells by C. parvum was dependent on IL-2 and IFN(s) produced in the culture. It was considered that M phi were important in the induction of LAK-like cells by C. parvum because the depletion of M phi from spleen cells before culture with C. parvum significantly reduced the induction of killer activity. The majority of effectors mediating both tumor cells and M phi were Thyl+ and asialo-GM1 (aGM1)+, and the lysis of M phi by C. parvum-induced killer cells could be inhibited by the addition of cold YAC-1 tumor cells and P815 tumor cells, suggesting that the same population of effectors recognized tumor cells and M phi. These results demonstrated a possibility that the killing of M phi by C. parvum-induced killer cells might down-regulate anti-tumor effects of C. parvum.
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PMID:Induction of murine lymphokine-activated killer-like cells by Corynebacterium parvum (C. parvum) in vitro: lysis of tumor cells and macrophages by C. parvum-induced killer cells. 158 May 62

Linomide (N-phenylmethyl-1,2-dihydro-4-hydroxyl-1-methyl-2-oxo-quinoline-3- carboxamide) is a quinoline 3-carboxamide which previously has been demonstrated to produce immunomodulator and antitumor effects when given in vivo. To test the possible antitumor effects of linomide against prostatic cancers, rats bearing five distinct Dunning R-3327 rat prostatic cancer sublines were treated daily with i.p. injections of linomide. These studies demonstrated that linomide has a reproducible antitumor effect against all of the prostatic cancers tested regardless of their growth rate, degree of morphologic differentiation, metastatic ability, or androgen responsiveness. This antitumor effect is observed only in vivo, not in vitro, and involves a cytotoxic response of the prostatic cancer cells. This cytotoxic response results in the retardation of the growth rate (i.e., increased tumor volume doubling time) of primary prostatic cancers and in metastatic lesions. Linomide's growth retardation is reversible, and thus continuous daily treatment with linomide is required for maximal antitumor response. Pretreatment of rats with linomide before tumor inoculation has no effect in addition to that produced by initiating linomide treatment at the time of tumor inoculation. No enhancement of either natural killer cell number or natural killer cell cytotoxic activity is induced by linomide treatment in the tumor-bearing rats. In addition, depletion of natural killer cell activity via injections of asialo-GM1 antiserum does not prevent the antitumor effects of linomide in vivo. Likewise, the antitumor effects of linomide are also produced in prostatic cancer-bearing athymic nude rats. These results suggest that the requirement for host involvement in the antitumor effects of linomide against rat prostatic cancers may involve both immune and nonimmune host mechanism(s) (e.g., antiangiogenesis).
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PMID:The antitumor effects of the quinoline-3-carboxamide linomide on Dunning R-3327 rat prostatic cancers. 159 18

The effect of murine recombinant interferon-gamma (IFN-gamma) on cell-mediated cytotoxicity against tumor cells in vitro and in vivo was investigated using a spontaneously developed, weakly immunogenic, syngeneic murine mammary adenocarcinoma, designated JC, as the target. Preincubation of JC tumor cells with IFN-gamma increased the susceptibility of lysis by both cytotoxic T lymphocytes and interleukin-2 (IL-2)-induced lymphokine-activated killer cells in an IFN-gamma dose-dependent manner. A direct injection of IFN-gamma (10,0000 U/d) daily for 5 consecutive days into the JC tumor nodule on the backs of BALB/c mice reduced the tumor growth in comparison with that of the control group. This antitumor activity was further enhanced by combination with a simultaneous intraperitoneal injection of IL-2 (300,000 IU/d) daily for 5 consecutive days. Phenotypic examination of tumor-infiltrating lymphocytes after injection of IFN-gamma plus IL-1 revealed an increased percentage of the cells expressing asialo GM1, L3T4, and IL-2 receptors. Additionally, an enhanced expression of major histocompatibility complex class I molecules on the JC tumor cells was detected. These results indicated that a direct injection of IFN-gamma into the tumor accompanied with the administration of IL-2, by enhancing cell-mediated immunity of the hosts and expression of major histocompatibility complex class I antigens on target cells, will be of potential clinical value.
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PMID:Enhanced cell-mediated cytotoxicity by interferon-gamma and interleukin-2 against syngeneic murine mammary adenocarcinoma. 162 74

Lethally irradiated C3H/HeN mice reconstituted with normal syngeneic bone marrow survived significantly longer than unmanipulated control mice following challenge with a lethal dose of 38C13 lymphoma cells 2 to 3 weeks post-bone marrow transplantation (BMT). Although the magnitude of this effect was modest, it was highly reproducible. This resistance-producing effect of BMT could be enhanced by interleukin 2 administration and could be abrogated by anti-asialo-GM1 antiserum treatment of recipients. These findings are consistent with the hypothesis that cells with a natural killer phenotype are activated by BMT and can mediate tumor resistance. These studies provide a model to explore the cellular basis, independent of donor alloreactivity, of the graft antitumor effect of BMT observed in humans.
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PMID:Tumor resistance induced by syngeneic bone marrow transplantation and enhanced by interleukin 2: a model for the graft versus leukemia reaction. 163 24

This study investigates the role of hepatic asialo GM1-positive cells in inhibiting hepatic metastasis of colon carcinoma (colon adenocarcinoma 38) in mice after administration of a biological response modifier, streptococcal derivative (OK432). Administration of OK432 increased the number of asialo GM1-positive cells in the liver, enhanced natural killer activity of hepatic mononuclear cells and reduced the number of hepatic metastases of colon carcinoma inoculated into the superior mesenteric vein. Administration of antiserum against asialo GM1 reduced the number of hepatic asialo GM1-positive cells, abolished natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases. In addition, administration of antiserum against asialo GM1 even after OK432 treatment also decreased the number of asialo GM1-positive cells, reduced natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases of colon carcinoma. However, administration of gadolinium chloride, which suppresses phagocytic function of Kupffer cells, did not influence the natural killer activity of hepatic mononuclear cells or the number of hepatic metastases. In vivo tumor-neutralization assay revealed that tumor growth was inhibited by the hepatic mononuclear asialo GM1-positive cells, but not by T lymphocytes or Kupffer cells after OK432 administration. These results suggest that an increased number of hepatic asialo GM1-positive cells after administration of OK432 plays an important role in protecting against metastasis of colon carcinoma in the liver.
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PMID:Inhibition of hepatic metastasis of colon carcinoma by asialo GM1--positive cells in the liver. 163 56

We have studied MAbs* for their ability to detect SCLC and differentiate this tumor type from the other lung tumor histotypes in cryostat sections of biopsy specimens taken at bronchoscopy from patients with suspected primary lung tumor disease. MAb F12, specific for the ganglioside fucosyl-GM1, reacted with 58% of the cases with SCLC (n = 19) and with less than 3% of those with non-SCLC (n = 38). MAb 123C3, specifically reactive with NCAM, reacted with 78% of the SCLC cases (n = 23). With this MAb no positive staining was seen in the non-SCLC cases (n = 41). None of the two MAbs reacted with tissue sections without tumor. In combined analysis with MAbs F12 and 123C3, all SCLC cases (n = 15) were positive with either and 47% with both of the MAbs. Our results show that both MAbs F12 and 123C3 are highly specific for SCLC in bronchoscopic biopsy tissue specimens, whereas the sensitivity for this histotype tends to be higher with MAb 123C3 than with F12 (P = 0.14). When used in combination, all SCLC cases could be identified. These MAbs may therefore be valuable as complements to current histopathologic characterization and differentiation of lung cancer.
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PMID:Immunohistochemical detection of two small cell lung carcinoma-associated antigens defined by MAbs F12 and 123C3 in bronchoscopy biopsy tissues. 165 59

Monoclonal antibodies (MAbs) reactive with the ganglioside fucosyl GM1 (Fuc-GM1), an antigen associated with small-cell carcinoma of the lung (SCLC), were tested for their ability to mediate tumor-cell killing in vitro in conjunction with humoral and cellular effectors and to inhibit tumor engraftment in nude mice in vivo. MAbs F12 and F15, both IgG3k, induced human complement-mediated cytolysis of 3 Fuc-GM1-expressing tumor cell lines: one rat hepatoma cell line, H4-II-E, and 2 human SCLC cell lines, NC1 H69 and NC1 H128. F12 and F15 also induced ADCC of these cell lines in the presence of either murine or human effector cells. Addition of sub-cytolytic amounts of fresh human serum as complement source resulted in enhanced ADCC induced by MAb F12 (IgG3). Also a Fuc-GM1-reactive MAb of IgM isotype, F9, was able to induce such complement-aided ADCC (CADCC). F12 and F15 both proved to effectively inhibit engraftment of H4-II-E tumors in nude mice. A single dose of a modest amount (40 micrograms) of MAb conferred 65 to 100% protection against development of tumors. Our results demonstrate that Fuc-GM1 can act as a target antigen on tumor cells for specific immunotherapy in vitro and in a mouse model in vivo. Complement and murine and human mononuclear effector cells were effective mediators of tumor cytolysis in vitro in the presence of murine Fuc-GM1-reactive MAbs. Our results also suggest that humoral and cellular effectors may co-operate in specific tumoricidal reactions and that these may be induced by antibodies of both IgG and IgM isotypes.
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PMID:Tumor-cell killing by MAbs against fucosyl GM1, a ganglioside antigen associated with small-cell lung carcinoma. 166 40

Peritumoral injection of recombinant human interleukin 1 beta (IL-1 beta) in mice transplanted subcutaneously with Friend erythroleukemia cells (FLC) resulted in a marked increase in survival time and inhibition of metastatic tumor growth in liver and spleen. In contract, IL-2 treatment alone did not significantly inhibit the development of FLC metastases. A synergistic antitumor effect was observed after combined IL-1/IL-2 therapy of these mice. The antitumor action of IL-1/IL-2 treatment was abolished or markedly reduced in mice treated with antibodies to CD4 or CD8 antigens, whereas antibodies to asialo-GM1 were ineffective. A clear-cut increase in the percentage of CD4+ cells was observed in the spleens of cytokine-treated mice on days 17 and 23. On day 23 of cytokine therapy, CD8+ cells were increased in both spleens and lymph nodes. On day 17, infiltrates of host-reactive cells (i.e., lymphocytes, granulocytes, and monocytes) were observed in both spleen and liver from FLC-injected mice treated with IL-1/IL-2, in association with tumor cells. On days 17 and 23, spleen cells and cells recovered from mesenteric lymph nodes of IL-1/IL-2-treated mice exerted a potent antitumor effect as determined by Winn assay experiments. This antitumor activity was abolished by preincubation of spleen cells with anti-CD8 antibody, but not by treatment with antibodies to asialo-GM1; antibodies to CD4 exerted only a slight effect. Combined IL-1/IL-2 therapy was more effective on established (i.e., 6-7-d) FLC tumors than on early (i.e., 1-d) tumor-transplanted mice. IL-1/IL-2 treatments were also highly effective in increasing survival time of mice from which the subcutaneous primary tumors were excised 7 d after FLC injection. These data indicate that in mice injected with FLC, the antitumor effects of IL-1/IL-2 are mediated by CD4+ and CD8+ cells (but not NK cells), and suggest that this combined cytokine treatment may be effective against established metastatic tumors.
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PMID:Combined interleukin 1/interleukin 2 therapy of mice injected with highly metastatic Friend leukemia cells: host antitumor mechanisms and marked effects on established metastases. 167 Oct 80

The report summarizes the work of our laboratory aimed at improving the understanding of the angiogenic response of adult tissues, an event that transforms a micro-embolus of neoplastic cells into a growing metastasis. Attention has been focused on tumor-induced angiogenesis. The following aspects of the subject are discussed: (a) relationship between size of vascular network and tumor growth rate or tumor cell population; (b) angiogenic capacity of tumors and role that prostaglandin E1 may have as an angiogenesis factor; (c) relationship between acquisition of angiogenic capacity and neoplastic transformation of a cell population; (d) modification of tissue composition at the onset of angiogenesis; (e) behaviour of copper ions and copper carriers in the course of the angiogenic response; (f) the influence of gangliosides on endothelial cell motility, survival and growth in vitro; (g) modulation of the angiogenic response by gangliosides (GM1, GT1b) in vivo.
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PMID:Gangliosides, copper ions and angiogenic capacity of adult tissues. 170 87

A Moloney virus-induced T cell lymphoma, YAC-1, derived from A/Sn (H-2a) inbred mouse origin, was tested for hybrid resistance (HyR) after subcutaneous (s.c.) or intracerebral (i.c.) tumor cell inoculation into syngeneic and semi-syngeneic mice. The F1 hybrids (H-2a/b) between A/Sn and C57BL/6 mice more strongly resisted the s.c. inoculation of 10(6) and 5 x 10(5) cells than did syngeneic recipients. In contrast, no HyR to the i.c. inoculation of 10(4) and 10(3) cells was seen in the F1 hybrid mice. Natural killer (NK) cell activity was much higher in F1 hybrids than in syngeneic mice. 125I-iododeoxyuridine-labeled YAC-1 cells were more efficiently eliminated from the highly resistant F1 hybrids than from the parental strain in both 4 and 18 hour in vivo rejection assays via intravenous (i.v.) and s.c. injection, respectively. The remaining radioactivity of the brain, however, did not differ between these mice. Thus, there was a correlation between the in vivo resistance of F1 hybrid mice to challenge s.c. inoculation of parental tumors and their expression of lymphocyte-mediated natural cytotoxicity in vitro against those tumors. T cell depletion by thymectomy followed by irradiation and fetal liver reconstitution did not abrogate the s.c. HyR against YAC-1, whereas NK cell depletion by i.v. administration of anti-asialo-GM1 antibodies resulted in the disappearance of the resistance. Furthermore, genotypic study segregating (A/Sn x C57BL/6) F1 x A/Sn backcross mice indicated that the s.c. HyR might be attributable primarily to heterozygosity within the H-2 complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cytotoxic effector mechanism and genetic control of non-immunized hybrid resistance to mouse T cell lymphoma transplanted outside and inside the brain]. 170 55


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