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

Minor H incompatible P815 tumor cells form progressively growing intraocular tumors when injected into the anterior chamber of eyes of BALB/c mice (an immunologically privileged site), but these tumor cells are promptly rejected when injected into the subconjunctival space. In both circumstances, the tumor inoculation site acquires significant numbers of DBA/2-specific precursor cytotoxic T cells (pTc) but only at the subconjunctival site do fully functional cytotoxic T cells (Tc) emerge, and their emergence coincides temporally with rejection of the tumor graft. In the present study, we wished to determine whether pTc can differentiate into Tc within the anterior chamber of the eye and whether the failure of BALB/c mice to reject intraocular P815 tumors is related to this putative block in pTc differentiation. It was previously shown that P815 tumor cells injected into the eyes of MHC-incompatible C57BL/6 mice are able to grow transiently within the anterior chamber and that they are eventually rejected. We have examined the local cytotoxic T cell responses during and after the transient phase of immune privilege that is extended to MHC-incompatible tumor grafts in eyes of C57BL/6 mice. Our results indicate that termination of immune privilege (rejection of the tumor implant) coincides with the detection of fully functional Tc within the tumor-containing eye. Circumstantial evidence suggests that these tumors are infiltrated with DBA/2-specific pTc during the phase of progressive tumor growth and that it is these infiltrating cells that differentiate in oculi into the Tc that effect graft rejection. These findings support the hypotheses that immune privilege in the anterior chamber of the eye is an actively maintained process that suppresses terminal differentiation of pTc and that privilege is abolished if conversion of pTc to Tc is accomplished.
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PMID:Termination of immune privilege in the anterior chamber of the eye when tumor-infiltrating lymphocytes acquire cytolytic function. 190 41

We have implicated histamine as a mediator of proliferation through its binding to novel intracellular receptors (HIC), closely associated with antiestrogen binding sites (AEBS) in microsomes and nuclei. N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE), is a potent ligand for AEBS/HIC. We now demonstrate that DPPE stimulates in vivo tumor growth (DMBA-induced mammary cancer in Sprague-Dawley rats and L5178Y leukemia in DBA/2 mice) and synergizes with phorbol-12-myristate-13-acetate (PMA) to induce inflammation and mitotic activity in mouse epidermis. Thus, ligands for intracellular histamine receptors may represent a new class of tumor promoting agents; this finding lends new credence to an important role for histamine in growth.
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PMID:Stimulation of in vivo tumor growth and phorbol ester-induced inflammation by N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine HCl, a potent ligand for intracellular histamine receptors. 193 Jan 76

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.
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PMID:Influence of the site of tumor growth on the capacity of a low tumorigenic line of Friend erythroleukemia cells to differentiate. 202 5

We have shown previously that the natural killer (NK) cell activity of DBA/2J mice bearing M-1 fibrosarcomas is consistently depressed at the later stages of tumor growth. The apparent mechanisms of inhibition are suppressor cell activation and prostaglandin E (PGE) production by tumor and lymphoid cells. In contrast, we show here that the natural cytotoxic (NC) activity of cells from the spleen, blood, and lymph nodes of mice bearing M-1 tumors is enhanced when compared to that of age- and sex-matched control mice. This enhanced NC activity does not appear to be due to increased cytolytic activity of macrophages but, rather, to enhanced cytolytic activity of multiple populations of non-adherent cells including B and T cells. Correlated with this is the finding that the NC activity of normal spleen cells is not inhibited in vitro by either PGE1 or PGE2 at levels which are inhibitory to NK cells. NC activity, although independent of PGE, is in fact enhanced by PGE1 in a dose-related fashion. These data indicate that NK and NC cells are regulated differently by PGE and during tumor growth. Utilizing a Winn assay, we also demonstrate that a cloned cell line with NC activity is capable of slowing tumor growth in vivo and that this action is improved if mice are treated with indomethacin concomitantly.
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PMID:Splenic natural cytotoxic activity is enhanced during growth of a murine fibrosarcoma. 234 16

It has been demonstrated by Parmiani et al. (Int. J. Cancer, 29: 323-332, 1982) that a significant protective effect can be obtained against the transplanted syngeneic YC8 lymphoma by prior immunization of BALB/c mice with normal allogeneic DBA/2 spleen cells. Using this well established tumor model, we investigated a novel approach, conditioning of specific immunotherapeutic activity. For this purpose, we used the odor of camphor as the conditioning stimulus and allogeneic DBA/2 spleen cells as unconditioning stimulus. We associated the conditioning and unconditioning stimuli two, three, and four times. Following this the conditioned animals were reexposed to the odor of camphor only. In each case, we observed a delay in tumor growth and in some instances the conditioned group performed better than the immunotherapy control group. These results indicate that a limited number of treatments with the antigen is better than the continuous treatment in maintaining the immunity and the homeostasis of the system.
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PMID:Conditioning: a new approach to immunotherapy. 236 86

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.
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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

Experiments were designed to test the presence of antitumor natural resistance (NR) in DBA/2 mice against highly oncogenic in vivo passaged histocompatible Friend leukemia cells (FLC-V). NR was measured in vivo as rapid clearance of radiolabeled cells from different organs or as growth inhibition in lethally irradiated mice. Interferon-sensitive (745) or interferon-resistant (3C18) lines were used. Organ clearance studies showed that young recipients eliminate cells more rapidly than old mice. Moreover, depressive (e.g., cyclophosphamide or carrageenen) or enhancing (e.g., poly (I:C) or Friend leukemia virus infection) agents of NR function modulate accordingly leukemia cell clearance. Similar results were obtained testing tumor growth in lethally irradiated hosts, although modulating agents were substantially less effective in this system. Both FLC-745-V and FLC-3C18-V lines were equally susceptible to NR. Therefore, these data provide further support to the hypothesis that exogenous IFN capable of suppressing the growth of both lines could act via enhancement of the NR function.
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PMID:Natural resistance in mice against Friend leukemia cells. II. Studies with in vivo passaged interferon-sensitive and interferon-resistant cell clones. 246 1

Previously we have described the isolation and characterization of a T-suppressor factor (TsF) from a T cell hybridoma (A10F), which has a degree of specificity for the DBA/2 mastocytoma P815. Administration of A10F intravenously at the time of tumor cell injection resulted in an accelerated rate of tumor growth, decreased cytotoxic T lymphocyte antitumor activity, and reduced survival time. In the work reported here, we have shown that administration of affinity-enriched A10F 7-14 days prior to tumor cell injection causes what appear to be reverse effects, in that an enhanced resistance to the P815 tumor is observed in vivo, an effect which we can correlate with the demonstration of antitumor cytotoxic T lymphocyte activity in vitro. These effects are dose-dependent since only doses of TsF at 20 micrograms or greater are effective. A similar effect was found when A10F was administered to DBA/2 mice 10 days prior to challenge with two unrelated tumors (L1210 and M-1). However, when another TsF (Fd11F) with apparent specificity for a nominal antigen was tested in this system, it had no effect on tumor growth.
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PMID:Preadministration of a T-suppressor factor enhances tumor immunity in DBA/2 mice. 249 88

A tumor model was developed in DBA/2 mice for studying the progression of the mastocytoma P 815 X 2 tumor. Tumor cells obtained from ascites were grown in vitro. The number of cells derived from a single clone was increased by in vitro culture. Cells were then injected either i.v. or i.p. into DBA/2 mice. Large volumes of tumor ascites were observed after i.p. but not i.v. injection. The latter led to tumor growth at multiple sites, especially in the liver. Mastocytoma cells were released from liver tissue and then injected i.p. into other recipients. For cloning of liver invading tumor cells, this procedure was repeated for greater than 20 generations of mice. Tumor infiltration of the liver increased strongly during this period, but ascites volume clearly decreased.
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PMID:Selection and isolation of a new variant of DBA/2 mastocytoma P 815 X 2. 251 87

This study investigates the potential of the alpha CD3-induced killer cells for use in adoptive immunotherapy of tumor growth. The alpha CD3-induced, activated, killer cells (CD3-AK) were generated in DBA/2 (H-2d) splenocytes by preactivation with alpha CD3 and were then cultured in the presence (CD3-AK [alpha CD3+]) or absence (CD3-AK [alpha CD3-]) of alpha CD3. The conventional lymphokine-activated killer (LAK) cells were induced by culturing DBA/2 splenocytes with purified human recombinant interleukin 2. Testing their in vitro cytotoxicity against syngeneic mastocytoma P815, CD3-AK (alpha CD3+) cells gave the highest levels of cytotoxicity and were 20-fold higher than LAK cells and 200-fold higher than CD3-AK (alpha CD3-) cells. However, the cytotoxic activity of LAK or CD3-AK (alpha CD3-) cells was augmented by preincubating them with alpha CD3 for 3 h; then, the difference in cytotoxic activity was reduced from 20- to 4-fold and from 200- to 2-fold, respectively. The in vivo antitumor activity of these killer cells paralleled the in vitro activity. In tests using tumor neutralization experiments, 80-100% of the mice that were challenged with 1 x 10(2) P815 cells remained tumor free after receiving 5 x 10(6) CD3-AK (alpha CD3+) cells. When the challenge dose increased to 1 x 10(3) and to 1 x 10(4) cells, giving CD3-AK (alpha CD3+) cells slowed down the rate of tumor growth but only 20% of the mice remained tumor free. The untreated LAK cells or CD3-AK (alpha CD3-) cells did not induce any protection. After preincubation with alpha CD3 for 3 h, the CD3-AK (alpha CD3-) cells provided protection in 30% of the challenged mice. The phenotype of effectors for mediating the in vitro and in vivo antitumor activities was found to be Thy1+, CD4-, and CD8+ cells. Flow microfluorometry analysis showed that the higher levels of cytotoxic activity obtained with CD3-AK (alpha CD3+) cells could not be simply explained by the increase of CD8+ cells, and the cytotoxic activity of individual CD3-AK (alpha CD3+) cells appeared to be much higher than that of the LAK cells. After tumor growth was established for 1-2 days, giving CD3-AK (alpha CD3+) cells slowed down the rate of tumor growth, and 20% of the mice remained tumor free. These results indicate that CD3-AK cells may be used in the immunotherapy of tumor growth.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vivo antitumor activity of anti-CD3-induced activated killer cells. 252 87


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