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)

Subcutaneous in vivo injections of cells of the mastocytoma line P815 in syngenic DBA/2 mice induce locally fast growing solid tumors. These have been used extensively as a cancer model to analyze and manipulate the relationship between tumor cells and host's immune defenses. We report that progression of P815 tumors in vivo was accompanied by a burst (Days 5-7) of local inflammatory cells recruitment and angiogenesis observed histologically, corroborated in vivo by MRI with gadolinium, overtranscription of macrophage activation marker genes, secretion of TNF-alpha by regional lymph node cells and concomitant systemic inflammation. No substantial overtranscriptions of either VEGF or IL-10 or TGF-beta genes were observed. Induction of COX-2 gene was a late event. To establish a possible relationship between the tumor-induced local, regional and systemic increase of pro-inflammatory mediators and progression of tumors in vivo, we carried out experiments deliberately modulating the inflammatory status of the recipient animals. Pretreatment of recipient animals by i.p. injection of thioglycolate accelerated P815 tumor growth. At the opposite, treatment of mice with either a COX-1 + COX-2 inhibitor (aspirin, 1 mg/day/mouse) or a specific COX-2 inhibitor (celecoxib, 0.13 mg/day/mouse) for 2 weeks after injection of tumor cells, significantly reduced the size and growth rate of tumors compared to control mice. Experiments carried out in vitro indicated that peritoneal macrophages from untreated animals were strongly activated by live P815 cells and by P815 membrane preparations. The tumor-induced inflammatory reaction could establish a local micro environment favoring tumor progression. The P815 tumor model might be helpful to recognize important factors controlling host/tumor relationship.
 ...
PMID:Inflammation and cancer, the mastocytoma P815 tumor model revisited: triggering of macrophage activation in vivo with pro-tumorigenic consequences. 1212 7

In murine tumors, innate immunity act as a trigger for the development of acquired immunity. The innate immune cells, natural killer (NK) and natural T (NKT) cells, generate the acquired immune cells, cytotoxic T lymphocytes (CTLs) and T helper (Th) 1 cells, by releasing interferon (IFN)-gamma. Regulatory T cells co-infiltrate with these tumoricidal effectors. In the innate phase, T cell receptor (TCR) gammadelta-bearing T (gammadelta T) and TCRalphabeta intermediate T cells are the regulators that suppress NK and NKT cells by elaborating interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-beta. The acquired phase has Th3/T regulatory 1-like cells that inhibit CTLs and Th1 cells by TGF-beta. Thus, cytokines from regulatory T cells exert profound effects on tumor growth.
 ...
PMID:Mechanisms of immune privilege for tumor cells by regulatory cytokines produced by innate and acquired immune cells. 1214 3

We previously demonstrated that Bothrops jararaca venom (BjV) has an antitumor effect on Ehrlich ascites tumor (EAT) cells and induces an increase of polymorphonuclear leukocytes in early stages of tumor growth. It has been reported that this venom presents an important inflammatory effect when inoculated in animal models and in human snakebites, and that cytokine levels have been detected in these cases. To evaluate whether the cytokines can be involved with the suppression of the tumoral growth, we evaluate the cytokine profile in the peritoneal cavity of mice inoculated with EAT cells and treated with BjV. Swiss mice were inoculated with EAT cells by the intraperitoneal route and treated with BjV venom (0.4 mg/kg, intraperitoneally), on the 1st, 4th, 7th, 10th, and 13th day. Mice were evaluated for cytokine levels on the 2nd, 5th, 8th, 11th and 14th day. Analysis was performed using an enzyme-linked immunosorbent assay for interleukin (IL)-1alpha, IL-2, IL4, IL-6, IL-10, IL-13, and tumor necrosis factor-alpha (TNF-alpha) levels in the peritoneal washing supernatant. Results were analyzed statistically by the Kruskal-Wallis and Dunn's tests at the 5% level of significance. We observed that EAT implantation induces IL-6 production on the 11th and 14th days of tumor growth, IL-10 on the 11th day and TNF-alpha on the 14th day. The treatment with BjV suppresses production of these cytokines. In addition, IL-13 was produced by animals that were inoculated only with venom on the 11th and 14th days, and by the group inoculated with EAT cells and treated with venom on the 2nd and 14th days. Furthermore, we suggest that the IL-6 detected in the present study is produced by the EAT cells and the suppression of its production could be associated with the antitumor effect of BjV.
 ...
PMID:Cytokine profile of Ehrlich ascites tumor treated with Bothrops jararaca venom. 1239 70

An IL-10 responsive signal protein, termed IL-10E1, was cloned from human prostate cancer PC-3 ML cells based on its binding affinity for a novel enhancer element (i.e., HTE-1: 5'-CACGATGACTCATCACTGTTGAAAGACA-3') of the Tissue Inhibitor of metalloproteinase-1 (TIMP-1) gene. Electrophoretic mobility shift assays (EMSAs) and enzyme linked immuno-sandwich assays (ELISAs) showed that IL-10 stimulated the rapid translocation of IL-10E1 to the nucleus and the activation of TIMP-1 expression in 4 different androgen dependent primary prostate tumor lines generated in our laboratory (i.e. HPCA-5a, 5b, 5c and 5d lines). IL-10 signaling was blocked by a variety of agents, including IL-10 receptor antibodies, alpha-toxin, and Genistein. The inhibition of IL-10 signaling and IL-10E1 expression correlated directly with a significant decrease in TIMP-1 expression by the HPCA-5a, 5b, 5c and 5d cell lines. Following permanent transfection of HPCA-5a and 5c cells with the IL-10 gene the growth of tumor xenografts in SCID CB17 mice was severely retarded, yielding tiny, poorly vascularized tumors by approximately 90 days post-inoculation s.c. ELISAs showed that these tumors expressed elevated levels of IL-10, IL-10E1 and TIMP-1 compared with tumors from non-transfected or Mock transfected cell lines. We conclude that the IL-10/IL-10 receptor axis (and IL-10E1 signaling) regulation of TIMP-1 expression plays a key role in inhibiting tumor growth, perhaps by blocking tumor vascularization.
 ...
PMID:IL-10/IL-10 receptor signaling regulates TIMP-1 expression in primary human prostate tumor lines. 1249 89

The proinflammatory cytokine interleukin (IL)-18 appears to be involved in the etiology of a variety of pathological conditions, among them rheumatoid arthritis and atherosclerosis as well as tumor growth and metastasis. As biological activity of matrix metalloproteinase-9 (MMP-9) has been identified as a hallmark in the pathogenesis of these diseases, effects of IL-18 on MMP-9 production by human peripheral blood mononuclear cells (PBMC) were investigated. Moreover, effects of immunopharmacological intervention by anti-tumor necrosis factor-alpha (TNFalpha) or IL-10 were evaluated. Here we report that IL-18 augmented production of MMP-9 by PBMC. The potency of IL-18 to induce release of MMP-9 from PBMC was comparable with that of TNFalpha. MMP-9 production was dependent on endogenous production of TNFalpha, as detected by use of neutralizing monoclonal antibodies. Whereas IL-18 and TNFalpha induced the protease, MMP-9 release was not mediated by IFNgamma. IL-18 also induced secretion of MMP-9 from human whole blood cultures. Antiinflammatory IL-10 efficiently downregulated release of MMP-9 from unstimulated and IL-18-activated PBMC. In contrast to MMP-9, secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) was not augmented by IL-18. Addition of IL-10 enhanced release of TIMP-1 from PBMC. The present study broadens the current pattern of IL-18 proinflammatory actions on PBMC, emphasizes the pivotal role of intermediate TNFalpha production in these responses, and relates IL-18 biological functions to the pathological role of MMP-9.
 ...
PMID:IL-18 initiates release of matrix metalloproteinase-9 from peripheral blood mononuclear cells without affecting tissue inhibitor of matrix metalloproteinases-1: suppression by TNF alpha blockage and modulation by IL-10. 1261 43

Human Flt3 ligand can expand dendritic cells (DC) and enhance immunogenicity in mice. However, little is known about the effects of murine Flt3 ligand (mFlt3L) on mouse DC development and function. We constructed a vector to transiently overexpress mFlt3L in mice. After a single treatment, up to 44% of splenocytes became CD11c(+) and the total number of DC increased 100-fold. DC expansion effects lasted for >35 days. mFlt3L DC were both phenotypically and functionally distinct. They had increased expression of MHC and costimulatory molecules and expressed elevated levels of B220 and DEC205 but had minimal CD4 staining. mFlt3L DC also had a markedly altered cytokine profile, including lowered secretion of IL-6, IL-10, IFN-gamma, and TNF-alpha, but had a slightly increased capacity to stimulate T cells in vitro. However, in a variety of in vivo models, DC expanded by mFlt3L induced tolerogenic effects on T cells. Adoptive transfer of Ag-pulsed mFlt3L splenic DC to naive mice actually caused faster rates of tumor growth and induced minimal CTL compared with control DC. mFlt3L also failed to protect against tumors in which human Flt3 ligand was protective, but depletion of CD4(+) T cells restored tumor protection. Our findings 1) demonstrate that mFlt3L has distinct effects on DC development, 2) suggest an important role for mFlt3L in generating DC that have tolerogenic effects on T cells, and 3) may have application in immunotherapy in generating massive numbers of DC for an extended duration.
 ...
PMID:Murine Flt3 ligand expands distinct dendritic cells with both tolerogenic and immunogenic properties. 1264 17

Sigma receptors are unique endoplasmic reticulum proteins that mediate signaling for a variety of drugs. We determined the effect of sigma(1) receptor agonists on immune responses in a syngeneic lung cancer model. Sigma(1) receptor agonists, including cocaine, up-regulated splenocyte IL-10 mRNA and protein production in vitro in a sigma receptor-dependent, pertussis toxin-sensitive manner. In vivo, sigma(1) receptor agonists promoted tumor growth and induced IL-10 at the tumor site. Increased tumor growth was prevented by administration of specific Abs to IL-10 or by administration of specific sigma(1) receptor antagonists. We report that sigma(1) receptor ligands, including cocaine, augment tumor growth through an IL-10 dependent mechanism.
 ...
PMID:IL-10 mediates sigma 1 receptor-dependent suppression of antitumor immunity. 1264 21

B7-H1 is a recently identified member of the B7 family molecules. Upon ligation to its receptors on T cells it regulates activation and differentiation of T cells. B7-H1 preferentially costimulates IL-10 production in resting T cells and further induces the apoptosis of activated T cells. PD-1 is a receptor of B7-H1 and is shown to mediate the inhibition of activated T cell response, presumably by inhibiting cell cycle progression. The expression of B7-H1 protein is limited to macrophage lineage of cells in normal tissues, although its mRNA transcription is found in a broad range of tissues. In contrast, B7-H1 is abundant in various human cancers. The tumor-associated B7-H1 increases apoptosis of antigen specific T cells, leading to growth of immunogenic tumor growth in vivo. Current data suggest that B7-H1 regulates the organ-specific tolerance in normal tissue and may contribute to immune evasion by cancers. Selective manipulation of B7-H1 pathway thus aids in the design of new regimens in the treatment of human autoimmune disease and the control of malignant cancers.
 ...
PMID:B7-H1 pathway and its role in the evasion of tumor immunity. 1272 64

Although many tumors express tumor-specific antigens, most fail to stimulate effective immune responses. Tumors generally lack co-stimulatory molecules, which can lead to tolerance of tumor-specific T cells and progressive tumor growth. Here, we demonstrate that the ovalbumin (OVA) transfected EL4 tumor, E.G7-OVA, grows progressively in syngeneic mice even though the tumor can be rejected if the mice are immunized with OVA in adjuvant. E.G7-OVA grew more rapidly in RAG-1 deficient than sufficient mice suggesting that normal mice make an abortive immune response to this tumor. Depletion of gammadelta T cells or IL-10 augmented the ability of B6 mice to reject E.G7-OVA. Spleen cells from normal, but not IL-10 knockout, mice reconstituted rapid tumor growth in gammadelta T cell-deficient mice. Thus, gammadelta T cells play an important role in preventing immune elimination of this tumor by a mechanism that directly or indirectly involves IL-10.
 ...
PMID:Inhibition of tumor rejection by gammadelta T cells and IL-10. 1274 51

Adjuvant arthritis (AA) is induced by immunizing Lewis rats with Mycobacterium tuberculosis suspended in adjuvant. The mycobacterial 65-kDa heat shock protein (HSP65) contains at least one epitope associated with the pathogenesis of AA: T cell clones that recognize an epitope formed by aa 180-188 of HSP65 react with self-cartilage and can adoptively transfer AA. Nevertheless, vaccination with HSP65 or some of its T cell epitopes can prevent AA by a mechanism that seems to involve cross-reactivity with the self-60-kDa HSP60. We recently demonstrated that DNA vaccination with the human hsp60 gene can inhibit AA. In the present work, we searched for regulatory epitopes using DNA vaccination with HSP60 gene fragments. We now report that specific HSP60 DNA fragments can serve as effective vaccines. Using overlapping HSP60 peptides, we identified a regulatory peptide (Hu3) that was specifically recognized by the T cells of DNA-vaccinated rats. Vaccination with Hu3, or transfer of splenocytes from Hu3-vaccinated rats, inhibited the development of AA. Vaccination with the mycobacterial homologue of Hu3 had no effect. Effective DNA or peptide vaccination was associated with enhanced T cell proliferation to a variety of disease-associated Ags, along with a Th2/3-like shift (down-regulation of IFN-gamma secretion and enhanced secretion of IL-10 and/or tumor growth factor beta1) in response to peptide Mt176-190 (the 180-188 epitope of HSP65). The regulatory response to HSP60 or its Hu3 epitope included both Th1 (IFN-gamma) and Th2/3 (IL-10/tumor growth factor beta1) secretors. These results show that regulatory mechanisms can be activated by immunization with relevant self-HSP60 epitopes.
 ...
PMID:DNA fragments of the human 60-kDa heat shock protein (HSP60) vaccinate against adjuvant arthritis: identification of a regulatory HSP60 peptide. 1450 Jun 49


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