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)

In a transplantable model of bladder cancer the inhibition of tumor growth by polyinosinic:polycytidylic acid (poly(I:C], concomitant stimulation of natural killer cell activity, and inhibition of both effects by prior inoculation with anti-interferon antiserum have been previously observed. The possible role of macrophages in these interactions is explored. Depletion of peritoneal macrophages by silica at concentrations that did not markedly depress natural killer cell activity was found to inhibit the enhancement of natural killer cell activity by subsequent in vivo poly(I:C) inoculation. Inoculation with silica also seemed to abrogate the tumor inhibitory effect of poly(I:C) treatment. To determine whether effects of poly(I:C) on natural cytotoxicity and tumor growth were mediated through production of interferon, anti-interferon antiserum (alpha-IF) was inoculated prior to poly(I:C) therapy. Tumor growth appeared to be uneffected by this maneuver even though poly(I:C)-induced enhancement of natural cytotoxicity was inhibited. Taken together, both macrophages and interferon may play a pivotal role in the immune response in both a stimulatory and a suppressive capacity. Additional study on such influences may be important if in vivo manipulation of these regulatory effects is to be accomplished successfully.
 ...
PMID:Macrophage depletion and manipulation of enhanced immune response in an animal model of bladder cancer. 619 5

The biology of the natural killer cell system is being investigated by many different laboratories using multiple approaches. The rationale for these investigations is the experimental evidence that NK cells play some role in inhibiting tumor growth and metastasis, convey some protective immunity and may be operative in control of differentiation from fetal life to adulthood. Thus, a survey of the literature reveals a multiplicity of studies examining many of these potential roles for NK cells. This review will attempt to summarize some of the findings critical to an understanding of the role NK cells play in immunophysiology and in immune reactions to various diseases. Even after ten years of study, the whole system of 'natural' reactivity remains difficult to define. The evidence available would indicate that the NK system while incompletely understood, may be manipulated in favor of the host when threatened by infectious or neoplastic disorders.
 ...
PMID:Natural killer cells: artifact to reality: an odyssey in biology. 637 59

The effects of human recombinant interferon-alpha 2 (IFN-alpha 2) and alpha-difluoromethylornithine (DFMO) as single agents and in combination were studied for efficacy against the renal cell adenocarcinoma (JDF-1) in an in vitro clonogenic assay and in vivo as xenografts in nude mice. In vitro studies showed dose-dependent inhibition of JDF-1 colony formation by IFN-alpha 2. DFMO alone did not significantly inhibit colony formation even though ornithine decarboxylase activity was significantly inhibited. The combination of IFN-alpha 2 and DFMO synergistically inhibited JDF-1 colony formation. The synergism was more readily observed at low IFN-alpha 2 concentrations. In vivo studies showed a similar tumor growth inhibition pattern. JDF-1 tumors were implanted s.c. in nude mice, and drugs were administered continuously by Alza minipumps (IFN-alpha 2) and in drinking water (DFMO) for 28 days. IFN-alpha 2 alone significantly inhibited JDF-1 growth, while DFMO alone had no significant inhibitory effect. The combination of IFN-alpha 2 and DFMO inhibited tumor growth in an apparent additive manner at the doses used. This was reflected in the mean tumor weights obtained at the termination of the experiment: control, 1484 +/- 187 (S.E.) mg; DFMO only, 1106 +/- 129 mg; IFN-alpha 2 only, 941 +/- 186 mg; and DFMO plus IFN-alpha 2, 620 +/- 109 mg. Assessment of mouse natural killer cell activity at the time of sacrifice showed that DFMO inhibited natural killer cell activity, while IFN-alpha 2 had no effect. DFMO was observed to inhibit ornithine decarboxylase activity in JDF-1 tumors by 78%, IFN-alpha 2 by 18%, and the combination by 78%. In addition, the drugs individually and in combination had similar inhibitory effects on JDF-1 spermidine content. One of the unexpected findings was the alteration in the spermine:spermidine ratio in the tumors treated with the combination of DFMO and IFN-alpha 2. The ratio in this group decreased to 0.44, while ratios for control, IFN-alpha 2 only, and DFMO only were 0.99, 0.66, and 0.88, respectively. These results clearly show that combined therapy with DFMO and IFN-alpha 2 is more effective than is single-drug therapy. The mechanism by which these drugs coordinately inhibit tumor growth is unclear but appears to be associated with direct inhibition of tumor cell proliferation, possibly by modulation of polyamine metabolism.
 ...
PMID:Effects of alpha-difluoromethylornithine and recombinant interferon-alpha 2 on the growth of a human renal cell adenocarcinoma xenograft in nude mice. 643 May 46

In this study, experiments were conducted to investigate immuno-modulating effects of bacillus Calmette-Guerin and poly I:C as determined by the cytotoxic activity of spleen and peritoneal exudates of C3H/HeN mice against MBT-2 target cells in vitro and the tumor growth patterns in vivo. It was found that animals receiving bacillus Calmette-Guerin exhibited most of the cytotoxic activity in the peritoneal exudate cells. On the contrary, animals receiving poly I:C exhibited most of the NK activity in the splenocytes and little or none in the peritoneal exudate cells. Administration of bacillus Calmette-Guerin or poly I:C in mice bearing small tumors (1 cm. mean diameter) resulted in an increased natural killer cell activity in the exudates and splenocytes of 65 and 50 per cent respectively. No cytotoxic activity was demonstrated when either of the 2 agents was administered to mice bearing large tumors. However, surgical excision of the tumor followed by bacillus Calmette-Guerin or poly I:C administration resulted in levels of natural killer cell activity comparable to those observed in tumor-free animals or in mice bearing tumors of 1 cm. in diameter.
 ...
PMID:The effect of tumor burden on the modulation of natural killer cell activity. 672 32

Immuno-chemotherapeutic effect on growth of 81B mammary tumor was studied in syngeneic C3H/He mice fed diet with low (D) or normal (N) protein content. 1. 5-FU 20 mg/kg. was given intra-peritoneal daily for 3 weeks. The tumor volume ratio (T/C) was significantly reduced on day 14 in both N and D-group mice. However, all mice were dead 2 weeks after administration of 5-FU in D-group mice. 2. Immuno-potentiator OK-432 (50 KE/kg,) or Lentinan (5 mg/kg,) was given i.p. daily for 3 weeks. The 81B tumor growth was inhibited on day 14 in N-group mice. However, the tumor growth was paradoxically accelerated after administration of these agents in D-group mice. Augmentation of the natural killer cell activity was recognized in N-group mice treated with OK-432 or Lentinan, but no change was seen in D-group mice. 3. After administration of 5-FU, intra-tumoral concentration of 5-FU was higher in N-group mice than that of in D-group mice.
 ...
PMID:[Effects of protein calorie intake on immuno- and chemotherapy]. 682 Sep 15

Mice challenged with L5178Y lymphoma cells expression high levels of the glycolipid asialo GM2 (gangliotriosylceramide) were protected from tumor growth by passive administration of a monoclonal antibody specific for the glycolipid; in a few antibody-treated mice, ascites cells eventually proliferated which contained a reduced chemical quantity of the glycolipid antigen (3). We now report that the cells emerging from antibody-treated mice had abnormal marker chromosomes identical to those in the cells used for challenge, indicating that the emergent cells were progeny of the challenge inoculum. Flow cytometric analysis revealed that asialo GM2 was undetectable on the surface of greater than 95% of the tumor cells from antibody-treated mice, whereas surface display of H-2 determinants was unchanged from that of the cells used for challenge. Tumor cells arising in challenged but untreated mice consisted of a mixture of asialo GM2-positive and -negative cells, indicating the presence of selective pressures in these mice as well. None of the cells taken from tumor bearing mice differed significantly from the challenge cells in their susceptibility to natural killer cell attack, suggesting that resistance to natural killer cell lysis was not responsible for the proliferation of these cells in vivo. When cells derived from an antibody-treated mouse were used to challenge mice, serotherapy with anti-asialo GM2 had no effect on mouse survival. These results suggest that serotherapy may complement a host anti-tumor response, from which only asialo GM2 deficient cells can escape.
 ...
PMID:Decreased glycolipid antigen expression in lymphoma cell variants escaping from anti-glycolipid serotherapy. 684 17

Prostaglandins (PGs) have been implicated as a regulator of tumor growth in mice and humans. Since natural killer cell (NK) cytotoxicity may be an important component of immune surveillance against cancer, it is appropriate to study whether the amount of PGs produced by tumors may be sufficient to suppress NK activity. Accordingly, the effect of various PGs on the NK activity of human peripheral mononuclear cells was investigated. The percentage cytotoxicity was measured by the release of Cr51 from labeled K562 and other target cells. At very high concentrations of PG (10(-6) M), suppression was seen with PGE2, PGD2, PGA2, and PGF2 alpha. However, at concentrations of PG in the physiologic range (10(-8) M), significant suppression was seen with PGE2 and PGD2 only. The percentage suppression with PGE2 ranged from 77% to 9.5% over a range of concentrations from 10(-5) to 10(-9) M (45% at 10(-8) M). Significant suppression was observed at 10(-8) M PGE2 with 4 different targets and at effector:target ratios varying from 50:1 to 12.5:1. To assess whether the suppressive effect of PGE2 was directed at the effector and/or target cell, K562 cells or effector cells were pretreated with PGE2. Significant suppression was seen with effector cell pretreatment but not with target cell pretreatment. Finally, the suppressive effects of supernatants obtained from tumor cell lines (polyoma virus-transformed murine fibroblast cell line, PY3T3) was determined. The marked suppressive effect of the supernatant could be attributed to its content of PGE. Thus, it appears that the production of PGE by tumor cells may be an important modulator of human NK activity.
 ...
PMID:The modulation of human natural killer cell activity by prostaglandins. 695 Oct 51

The ultraviolet radiation-induced fibrosarcoma 1591 generally is rejected by normal syngeneic mice and only rarely exhibits progressive growth. We isolated five of these rare progressor tumors from normal animals to determine the selective pressures that had been exerted upon the parental tumor by normal immunocompetent hosts. We found that the variant tumor cell lines could neither induce nor be killed by tumor-specific lymphocytes, suggesting that selection had been exerted against tumor cells expressing the tumor-specific antigen. In contrast, no selection against natural killer cell activity or against nonspecific T cell-mediated immunity seems to have occurred because progressor tumor cells were highly sensitive to these types of effector cells and in fact induced these effector cells more effectively than did the parental tumor. Nude mice were found to be as capable as normal mice in generating natural killer activity in response to a challenge with progressor tumor cells, but they were unable to mount a nonspecific T lymphocyte response. This may account for the fact that the progressor tumors grew at a significantly faster rate in nude animals than in normal mice. Thus, our study shows that in this tumor system nonspecific T cell-mediated immunity may play a role in retarding tumor growth, but the absolute resistance of normal animals to progressive tumor growth critically depends upon the presence of T cell-mediated tumor-specific immunity. Furthermore, neither NK cells nor nonspecific cytotoxic T lymphocytes appear to play a role in immunoselection against this tumor in normal immunocompetent hosts.
 ...
PMID:Mechanisms of syngeneic tumor rejection. Susceptibility of host-selected progressor variants to various immunological effector cells. 697 9

Progressive tumor growth is associated with a state of immunosuppression. One mode of immunosuppression is thought to be mediated by immunosuppressive factors of tumour origin. We have investigated in vitro the possibility that suramin could be used to blockade tumor derived suppressor factors and enhance the effectiveness of rhIL-2 therapy. These data show that factors derived from cultures of the colorectal carcinoma cell line LoVo suppressed the percentage of cells expressing the natural killer cell antigen CD56 in 92% of individuals and the cytotoxic T cell antigen CD8 in 77% of individuals tested from a panel of 13 normal healthy volunteers. Suramin at 200 micrograms/ml restored the percentage of cells expressing CD56 to levels higher than the control cultures and reduced the suppression in those expressing CD8 to non-significant levels. LoVo produced factors also suppressed the expression of the activation associated antigens CD25, CD71 and HLA-Dr with suramin restoring CD25 expression but not CD71 or HLA-Dr. Functional studies using 51Cr-release assays showed that LoVo produced factors could suppress cytotoxicity in 46% of individuals tested, and of these a reduction in suppression by suramin was demonstrated in 50% of individuals against Daudi target cells and 33% against K562 target cells.
 ...
PMID:Colorectal cell line suppression of lymphokine activated killer cell generation is reversed by suramin. 754 Aug 93

This study addresses the role of MHC class I molecules in the rejection of tumor grafts by SCID mice. Tumor cell lines, their corresponding MHC class I transfectants, and MHC class I-deficient mutants were inoculated to SCID mice. This allowed a study of tumor rejection responses in an environment with normal numbers of natural killer cells but largely devoid of functional T and B cells. C.B-17 (H-2d) SCID mice were found to reject low (10(2)) but not high (10(4)) doses of allogeneic (H-2b) tumor cells. The introduction of H-2Dd into such allogeneic tumor cells abrogated the rejection response with progressive tumor growth as a consequence. Introduction of H-2Kd or Ld had no or only marginal effects. The protective ability of H-2Dd was mapped to the alpha 1/alpha 2 domains of the molecule. H-2Dd protected allogeneic tumors from rejection also in C3H SCID mice of the H-2k haplotype, demonstrating that this ability was not dependent on H-2Dd expression in the host. Expression of endogenous H-2Kb and/or Db molecules partially protected wild-type allogeneic tumor cells from rejection since mutant allogeneic cells, devoid of class I expression, were rejected even after high-dose inoculation. Introduction of either allogeneic or xenogeneic class I molecules did not lead to rejection of otherwise MHC class I syngeneic (H-2d) tumor cells. The observed tumor cell rejection in SCID mice was dependent on natural killer cells. After depletion of asialo-GM1+ cells, all inoculated tumor cell lines grew progressively, independently of MHC class I expression. These results are compatible with a model where expression of certain, but not all, class I molecules protect from natural killer cell-mediated rejection. There was no evidence for rejection occurring as a consequence of the expression of allogeneic or xenogeneic class I molecules on the grafted cells. MHC class I expression may thus influence tumor cell recognition in mice lacking T-cell receptor expression.
 ...
PMID:Rejection of tumors in mice with severe combined immunodeficiency syndrome determined by the major histocompatibility complex. Class I expression on the graft. 772 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>