UMLS:C0598934 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0598934 (tumor growth)
58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative and functional methods were used to assess changes in NK (ASGM-1+, nonblast, lymphoid) cells and cytotoxic/suppressor T (Lyt-2+) cells in the spleen and bone marrow (BM) of normal DBA/2 mice and/or mice bearing early (7 days)- and late (14 days)-stage erythroleukemia +/- concomitant oral administration of indomethacin. In normal mice, indomethacin increased ASGM-1+ cells in the spleen and BM by 7 days of continuous drug administration relative to control, while the numbers of Lyt-2+ cells in both organs remained unaltered. The presence of a tumor in untreated mice resulted, by 14 days development, in elevated numbers of ASGM-1+ cells in the spleen and BM. Lyt-2+ cells in the spleen increased transiently (7 days) in tumor-bearing (TB) mice and returned to normal levels by 14 days TB. No difference in either early- or late-stage TB was observed in the numbers of Lyt-2+ cells in the BM. In spleen and BM of TB mice, indomethacin increased ASGM-1+ cells by 7 days TB. ASGM-1+ cells returned to untreated levels by 14 days TB in both organs in spite of continued drug treatment. The numbers of Lyt-2+ cells in both the spleen and BM of 7 days indomethacin-treated TB mice were reduced relative to those of untreated TB mice. By 14 days TB, drug treatment had no effect on Lyt-2+ cell numbers in the spleen or BM. Spontaneous cytolytic activity of the spleen and BM did not always parallel changes in the numbers of ASGM-1+ cells, indicating the presence of late, immature, prelytic NK cells among the ASGM-1+ cell numbers. The results demonstrate that the numbers of NK and cytotoxic/suppressor T cells are markedly but differentially affected during tumor growth and/or time of exposure to indomethacin in an organ-specific manner.
...
PMID:Population dynamics of natural killer cells and T lymphocytes in murine spleen and bone marrow during the development of erythroleukemia: the effect of indomethacin. 149 21

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.
...
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

Friend erythroleukemia cells (FLC) passaged in mice are highly tumorigenic and multiply extensively in the livers of suckling DBA/2 mice without differentiating. In contrast, in vitro passaged FLCs injected intravenously were of low tumorigenicity, multiplied to a limited extent in the livers of suckling mice, and underwent marked differentiation from the proerythroblast to the orthochromatic erythroblast stage in the liver. The presence of characteristic C-type virions budding from the cell surface in various stages of erythroid differentiation served as a marker of the injected FLCs. When the same in vitro passaged FLCs that differentiated in the liver were injected subcutaneously in suckling mice, they formed large subcutaneous tumors consisting of sheets of undifferentiated tumor cells. It is concluded that the tumorigenicity of FLCs depended on the site of tumor growth and that there is an inverse correlation between the tumorigenic capacity and the capacity to differentiate.
...
PMID:Influence of the site of tumor growth on the capacity of a low tumorigenic line of Friend erythroleukemia cells to differentiate. 202 5

The in vivo differentiation-inducing activity of a purified human erythroid differentiation factor (EDF) toward mouse erythroleukemic cells (MEL cells) was examined. BDF1 mice with diffusion chambers implanted in the peritoneal cavity were treated with continuous i.p. administration of EDF. MEL cells within a diffusion chamber differentiated into hemoglobin-positive cells when treated with EDF, the percentage of the positive cells being 32.3 +/- 28.3 on day 5 as compared to 0.2 +/- 0.3 in the controls. The anti-tumor activity of EDF was also examined in a nude mouse MEL solid tumor model. Daily intra-tumor treatment with EDF for 10 days resulted in 73% suppression of tumor growth on day 25. A histological study revealed that EDF-treated solid tumor cells became hemoglobin-positive, indicating the anti-tumor activity of EDF through induction of differentiation in vivo. EDF could induce in vitro the differentiation of human erythroleukemic cell lines K562 and HEL, as well as the murine cell line. These results indicate the possibility of differentiation therapy for erythroleukemia using EDF.
...
PMID:Differentiation-inducing and growth-inhibitory activities of erythroid differentiation factor (EDF/activin A) toward mouse erythroleukemic cells in vivo. 232 49

Thirty-two murine monoclonal antibodies (MAbs) against the external domain of the human transferrin (Tf) receptor have been obtained using human Tf receptor glycoprotein produced in a baculovirus expression system as immunogen. The MAbs were tested separately, and in combination, for their ability to inhibit growth of CCRF-CEM leukemic T-cells in tissue culture. One MAb, D65.30, an IgG1, inhibited growth of CCRF-CEM cells as effectively as the anti-Tf receptor MAb 42/6, an IgA, previously found to have the highest antiproliferative activity in this assay. Some combinations of two or more MAbs inhibited the in vitro growth of CCRF-CEM much more effectively than single MAbs. Eleven IgG1 anti-Tf receptor MAbs, when combined individually with D65.30, increased the inhibition of CCRF-CEM growth from approximately 65% to greater than 90% in a 7-day growth assay. Similarly, many IgG MAbs in combination with 42/6 also inhibited CCRF-CEM growth by greater than 90%. The growth-inhibitory effects of certain combinations of MAbs were clearly synergistic, because either one or both MAbs tested separately were inactive. These pairs of MAbs also inhibited the growth of HL-60 and KG-1 leukemic cells by greater than 90% and partially inhibited the growth of K562 erythroleukemia and M21 melanoma cells, which are resistant to MAb 42/6. However, not all combinations of anti-Tf receptor MAbs were more effective; eight MAbs markedly antagonized the antiproliferative effects of D65.30, whereas 12 others had little or no effect. Preincubation of HL-60 cells with three different pairs of MAbs, D65.30 and A27.15, B3/25 and 42/6, and B3/25 and TR3A, inhibited subsequent colony formation by greater than 95%, demonstrating that their action is cytotoxic, not cytostatic. The antiproliferative activity of these pairs of MAbs correlates with their ability to block Tf-mediated 59Fe uptake and perturb Tf receptor expression. Treatment of nude mice bearing established s.c. CCRF-CEM tumors with a combination of MAbs D65.30 and A27.15 inhibited tumor growth and in some animals led to complete tumor regression. Each MAb administered separately was much less effective. We conclude that combinations of two or more anti-Tf receptor MAbs can interact synergistically to inhibit cell growth in vitro and tumor growth in vivo.
...
PMID:Combinations of anti-transferrin receptor monoclonal antibodies inhibit human tumor cell growth in vitro and in vivo: evidence for synergistic antiproliferative effects. 240 Sep 93

Adult DBA/2 mice were given injections s.c. with either interferon-sensitive (745) or -resistant (3Cl-8) Friend erythroleukemia cells (FLC). After tumor nodules had developed, mouse interferon-alpha/beta was injected daily into the tumor. 31P-Nuclear magnetic resonance (NMR) spectroscopy examinations were undertaken on freshly dissected tumors at different days of treatment with either interferon or control preparations. Analysis of 745 FLC tumors in untreated mice at different days of tumor growth (day 8 to 13 after tumor implantation) showed marked increases in the levels of phosphorylcholine (PCho), glycerophosphorylethanolamine (GroPEtn) and glycerophosphorylcholine (GroPCho). In contrast high levels of PCho, GroPEtn and GroPCho were already detectable in the 3Cl-8 FLC tumors on day 8, and no significant changes were observed during subsequent tumor growth. The intracellular pH value remained practically constant in both FLC tumors. Daily intratumoral administration of either partially purified (10(7) IU/mg of protein) or highly purified (10(9) IU/mg of protein) mouse interferon-alpha/beta to both cell tumors resulted in decreases in the levels of PCho, GroPEtn and GroPCho and in increases in the intracellular pH with respect to tumors treated with control preparations or left untreated. Two days of daily treatment of mice with interferon sufficed to induce these metabolic changes which preceded the appearance of necrosis in the tumors. Treatment of FLC tumors with X-rays on day 12 of tumor growth did not result in any comparable metabolic changes 2 days after irradiation. Changes in the levels of phospholipid metabolites were not observed when 745 or 3Cl-8 cells were cultivated in the presence of interferon. As interferon induced these changes in both interferon-sensitive and -resistant tumors we conclude that interferon treatment results in host-mediated effects on the biosynthesis and/or catabolism of tumor cell phospholipids.
...
PMID:31P-nuclear magnetic resonance analysis of interferon-induced alterations of phospholipid metabolites in interferon-sensitive and interferon-resistant Friend leukemia cell tumors in mice. 242 86

Peri-tumoral injection of recombinant human interleukin-1 beta in mice transplanted s.c. with Friend erythroleukemia cells (FLC) resulted in marked inhibition of tumor growth and increased survival. However, in vitro treatment of FLC (745 or 3Cl-8) with IL-1 beta barely inhibited cell multiplication. IL-1 beta, injected into established solid tumors, induced marked morphologic changes. Vascular congestion and focal extravasation of erythrocytes were observed as early as 6 hr after injection with IL-1 beta of FLC and L1210 tumors and HeJ16 fibrosarcomas. Focal areas of disaggregation of tumor cells and tumor necrosis were observed 6 and 24 hr after IL-1 injection. These morphologic changes were similar to those observed in FLC tumors or HeJ16 fibrosarcomas treated with TNF-alpha or beta. These cytokines determined morphological changes in tumor blood vessels of FLC tumors within 1 hr of injection. Freshly dissected FLC tumors and their tissue extracts were studied by Nuclear Magnetic Resonance (NMR) spectroscopy, shortly after peri-tumoral injection of IL-1 beta or TNF-beta. After 6 hr, both cytokines induced a 3-fold reduction in the levels of two catabolites, glycerophosphorylcholine and glycerophosphorylethanolamine, an accumulation of sn-glycerol 3-phosphate and a more than 10-fold increase in the choline/phosphorylcholine ratio. These results are similar to those reported for TNF-alpha, and can be interpreted on the basis of an activation of glycerophosphorylcholine phosphodiesterase (EC 3.1.4.2) and partial inhibition of choline kinase (EC 2.7.1.32). IL-1 beta and TNF-beta (like TNF-alpha) also induced alkaline shifts (0.10-0.25 units) in the average intratumoral pH value. We suggest that alterations of tumor blood vessels may be the primary events in solid tumors treated with IL-1 beta or TNF. Such alterations lead to early changes in tumor metabolism and subsequent tumor cell degeneration.
...
PMID:Interleukin-1 beta induces tumor necrosis and early morphologic and metabolic changes in transplantable mouse tumors. Similarities with the anti-tumor effects of tumor necrosis factor alpha or beta. 278 94

DBA/2 mice were injected sc with cells from the highly malignant Friend erythroleukemia cell (FLC) 3Cl8 subline, which is resistant to mouse interferon alpha/beta, or with the ESb lymphoma. When interferon alpha/beta was injected intratumorally or peritumorally, tumor growth was markedly suppressed, and established vascularized tumor nodules became progressively necrotic. Tumor necrosis was of the coagulation type that usually results from deprivation of blood flow. Morphologic examination of approximately 1,000 blood vessel profiles and approximately 2,000 endothelial cells in 1-micron Epon sections of sc 3C18 FLC tumors showed that interferon treatment resulted in rapid and pronounced vascular endothelial cell damage that preceded tumor necrosis. No inflammatory cell infiltrate was observed. Our results suggest that interferon alpha/beta exerted an antitumor effect in these tumor models by damaging tumor blood vessels, causing disruption of tumor blood flow, which led to ischemic tumor necrosis.
...
PMID:Microvascular injury in pathogenesis of interferon-induced necrosis of subcutaneous tumors in mice. 292 74

Friend erythroleukemia cells (FLC) (H-2d) injected intravenously into adult syngeneic DBA/2 or allogeneic C57B1/6 (H-2b) or C3H (H-2k) mice lodge in the liver but only multiply in the liver of syngeneic mice. Our results indicated that endogenous IFN-alpha/beta was a crucial factor in preventing the multiplication of FLC in the liver of adult allogeneic mice. (a) Treatment of allogeneic adult C57B1/6 or C3H mice with polyclonal antibody to mouse IFN-alpha/beta (but not antibody to IFN-gamma) completely abrogated the resistance to the multiplication of FLC in the liver and 87% of tumor-injected, antibody-treated C57B1/6 mice died with extensive tumor involvement of the liver. In contrast, after intravenous inoculation FLC do not multiply at all (or very rarely) in the liver of adult C57B1/6 mice left untreated or treated with a variety of control globulins, and no deaths occurred. (b) 8 h after intravenous inoculation of FLC, poly(A)+ RNA hybridizable with specific DNA probes for mouse IFN-alpha or -beta (but not -gamma) was present in the liver of injected C57B1/6 mice. Using the expression of the Mx protein as an indicator of the presence of IFN-alpha/beta, we showed that Mx+ congenic C57B1/6 mice injected with FLC exhibited a marked increase in the expression of the Mx protein in the liver, spleen, kidney and lung, and this increase was blocked by treatment of mice with antibody to IFN-alpha/beta. The possibility that different host mechanisms are elicited depending on the site of tumor growth in allogeneic mice is discussed. IFN-alpha/beta appears to be of particular importance in determining the resistance of the liver to FLC in allogeneic mice.
...
PMID:Antibody to mouse interferon alpha/beta abrogates resistance to the multiplication of Friend erythroleukemia cells in the livers of allogeneic mice. 317 80

We previously showed that immunotherapy using indomethacin combined with rIL-2 in vivo was very effective in stimulating natural killer (NK) cells and in increasing the life span of young adult mice bearing a tumor of hemopoietic origin. The aim of the present study was to test the efficacy and universality, with respect to age, of this treatment in tumor-bearing mice. DBA/2 mice (10-16 months old) were injected with 5 x 10(6) erythroleukemia cells and remained either: (i) untreated (control); (ii) treated with indomethacin (5 micrograms/ml drinking water) for 9 days from tumor onset; (iii) treated with rIL-2 (24 x 10(3) U/injection) twice a day for the last 4 days of the 9-day tumor-bearing period, or (iv) treated with both indomethacin and rIL-2 concomitantly. Some mice from each group (above) were killed after 9 days of tumor growth, while the others were allowed to survive. Spleen and bone marrow cells were collected from the mice of each group and NK (ASGM-1+) cells were quantitated using an immunoperoxidase technique combined with light microscopy. NK cell-mediated activity was assessed using a standard chromium release assay. The results show that although NK cell numbers increase in the presence of the growing tumor, neither indomethacin alone, rIL-2 alone, nor the combination could further increase the numbers of these cells. Furthermore, indomethacin and/or rIL-2 could not induce NK cell-mediated activity in such mice. Moreover, tumor-bearing aged mice treated as above did not have a significantly longer life span than untreated (control) tumor-bearing mice. The present results indicate an age-dependent resistance to a form of immunotherapy already proven very effective in young adult mice. Furthermore, the results of this and our previous studies suggest that immunotherapy, which may be highly effective in one age group, should not be presumed effective throughout life.
...
PMID:Effectiveness of immunotherapy in aged leukemic mice. 755 96

1 2 3 Next >>