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)

CD4(+)CD25+ T regulatory (Treg) cells have been shown to critically regulate self and allograft tolerance in mice. Studies of human Treg cells have been hindered by low numbers present in peripheral blood and difficult purification. We found that cord blood was a superior source for Treg-cell isolation and cell line generation compared with adult blood. Cord blood CD4(+)CD25+ cells were readily purified and generated cell lines that consistently exhibited potent suppressor activity, with more than 95% suppression of allogeneic mixed lymphocyte reactions (MLRs) (29 of 30 donors). Cultured Treg cells blocked cytokine accumulation in MLRs, with a less robust inhibition of chemokine production. These cell lines uniformly expressed CD25, CD62L, CCR7, CD27, and intracellular cytotoxic T-lymphocyte antigen-4 (CTLA4). FoxP3 protein, but not mRNA, was specifically expressed. Upon restimulation with anti-CD3/CD28 beads, the cultured Treg cells produced minimal cytokines (interleukin-2 [IL-2], interferon-gamma [IFN-gamma], and IL-10) and preferentially expressed tumor growth factor-beta (TGF-beta) latency associated protein. Cytokine production, however, was restored to normal levels by restimulation with phorbol myristate acetate (PMA)/ionomycin. Cord blood-derived cultured suppressor cell function was predominantly independent of IL-10 and TGF-beta. These results demonstrate cord blood contains a significant number of Treg precursor cells capable of potent suppressor function after culture activation. Banked cord blood specimens may serve as a readily available source of Treg cells for immunotherapy.
...
PMID:Cord blood CD4(+)CD25(+)-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function. 1537 87

CD4(+)CD25(+) T cells are an important population that plays a crucial role in the maintenance of peripheral self-tolerance. Recently, it was shown that the elimination of these cells by in vivo administration of anti-CD25 monoclonal antibody (mAb) caused the regression of highly immunogenic tumors in syngeneic mice. In this study, we examined whether B16F10 melanoma cells regressed with the elimination of CD25(+) regulatory T cells. We found the melanoma cells were not affected at all by in vivo anti-CD25 mAb administration alone but tumor rejection resulted in all mice when the administration was combined with IL-12 gene transfer to tumor cells. In vivo, depletion of natural killer (NK) cells or CD8(+) T cells cancelled the tumor rejection. NK-cell depletion allowed IL-12-transfected B16F10 melanoma (B16/IL-12) to grow from an early stage and resulted in a more rapid tumor growth of B16/IL-12 than that in mice without administration of anti-CD25 mAb. On the other hand, CD8(+) T-cell depletion did not affect the tumor growth in the early phase but allowed B16/IL-12 to grow in rather a late phase and resulted in almost the same degree of tumor growth as in mice without administration of anti-CD25 mAb. In a previous study, we showed that the elimination of CD4(+) T cells enhanced the antitumor effect of B16/IL-12 and induced vitiligo-like coat color alteration. Therefore, we also examined the frequency of the change to a vitiligo-like coat color in mice showing tumor rejection caused by CD25(+) T-cell elimination to compare with the mechanism enhancing the antitumor effects by cell elimination. The elimination of CD25(+) T cells did not induce vitiligo-like coat color changes, though that of CD4(+) T cells induced the change in 60% of mice. Furthermore, we confirmed that elimination of CD25(+) T cells did not affect the T-helper (Th) 1/Th2 cytokine profile, while that of CD4(+)T cells abrogated the Th2 cytokines (IL-4 and IL-10) and resulted in a Th1-dominant cytokine profile in the tumor-draining lymph nodes (TDLNs) of B16/IL-12-bearing mice. These results indicate that in vivo depletion of CD25(+) regulatory T cells is a potent useful adjuvant in immunotherapy of B16F10 melanoma, when combined with IL-12 gene transfer and that the enhancement of the antitumor effect by CD25(+) T-cell depletion is mediated through CD8(+) T cells and may differ from the enhancing mechanism caused by CD4(+) T-cell depletion.
...
PMID:In vivo elimination of CD25+ regulatory T cells leads to tumor rejection of B16F10 melanoma, when combined with interleukin-12 gene transfer. 1544 21

Bacterial endotoxins such as Escherichia coli lipopolysaccharide (LPS) bind to specific Toll-like receptors in fixed and circulating immunocompetent cells and activate the sympathetic and pituitary-adrenal system through similar receptors in cells that form the blood-brain interface. The latter, in turn, lead to the formation, within the brain, of proinflammatory cytokines including interleukin (IL)-1alpha, IL-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), and one or more antinflammatory cytokines including tumor growth factor beta (TGF-beta), and IL-10. Although the full panoply of central cytokines can be activated after systemic exposure, direct introduction of IL-1beta into the brain exerts a unique pattern of peripheral immune responses attributable to the special properties of reactive cells within the brain and to the "reservoir" function of the cerebrospinal fluid compartment. De Simoni et al. were the first to show that the intracerebroventricular (icv) injection of IL-1beta in rats induced a dramatic increase in the concentration of circulating IL-6 that was much greater and more prolonged than that induced by intravenous bolus injection of the same dose of cytokine. The work reported in this paper shows that the "De Simoni paradox" is mainly due to the prolonged release of the injected IL-1beta from brain to blood: a large proportion is not degraded (86%), transport out is both active and passive, and the initial exposure to IL-1beta sensitizes peripheral responses to the continuing exposure to the cytokine. Although IL-6, TNF-alpha and LPS are passively transferred from brain to blood (as shown by radioiodine-labeled tracer studies) peripheral cytokine responses to central injection differ from responses to IL-1beta. Peripheral responses to central TNF-alpha are similar to those after peripheral administration because TNF-alpha has no peripheral sensitizing effect. Peripheral response to central LPS exposure is much less than that which occurs when an amount identical with that transferred from brain to blood is administered peripherally. This is due to the fact that intracerebral injection of LPS suppresses response to peripherally administered endotoxin. Since the effect can still be demonstrated in adrenalectomized animals maintained on a constant dose of corticosterone, the brain has the capacity by as yet undefined mechanisms to suppress peripheral inflammatory responses.
...
PMID:Neuroendocrinology of acute immunity. 1548 3

Several lines of evidence from recent years support the existence of cancer immunosurveillance, especially studies of natural killer (NK) cells and the IFN-gamma pathway. However, immune suppression is clearly observed in cancer patients and tumor-bearing animals as well. The fact is that although cancers often elicit a vigorous immune response during the early part of their growth, the immune response is soon down-regulated, permitting progressive tumor growth. Apparently, the intrinsic plasticity of tumors allows the immune system to sculpt the immunogenic phenotypes of tumors to escape efficient immune destruction. But most evidently, several mechanisms have now been found to contribute to the failure of immune control of tumor growth. Tumor cells have a very low level of MHC class II, costimulatory molecules, and weak antigens. They also produce immune suppressive factors (VEGF, IL-10, PGE(2)) that exert systemic effects on immune cell function. In particular, disabled dendritic cell differentiation, maturation, migration, and function are fundamental to this defect, as they are the most potent antigen-presenting cells (APCs) of the immune system, interacting with T and B lymphocyte as well as NK cells to induce and modulate immune responses. In addition, tumors also alter host hematopoiesis and produce large numbers of immature dendritic cells, and evidence shows that these cells are directly immune suppressive. Harnessing the immune system for effective cancer therapy has remained a great challenge. DC-based vaccines, or DC-based vaccines in combination with treatments designed to improve the host immune environment, may offer hope for more effective cancer immunotherapy. Tumor-host interactions are an important determinant of tumor behavior and response to therapy. How tumors interact with their hosts is thus a very broad and complex topic. In this chapter, we will focus on tumor-host immune interactions and the roles of dendritic cell dysfunction in tumor avoidance of host immune responses. We will survey recent findings regarding tumor immune surveillance, antitumor host immune responses, and how the immune system also functions to promote or select tumor variants with reduced immunogenicity. We will then discuss immune suppression caused by tumors, which is clearly observed in tumor-bearing animals and cancer patients. Finally, we will discuss altered dendritic cell function and differentiation in some detail, as it is likely to be one of the most fundamental mechanisms by which tumors escape immune responses.
...
PMID:Tumor-host immune interactions and dendritic cell dysfunction. 1553 May 55

Results from a limited number of studies suggest a potential role for endogenous histamine in regulating tumor growth in immunocompetent cells. The present study examined the effects of exogenous histamine on colorectal cancer growth and the immune response against tumor tissue in mice. Histamine was administered for 21 days to Colon 38 mouse colon adenocarcinoma-implanted syngeneic mice and tumor volume was measured throughout the experiment. Systemic administration of histamine for 21 days caused a significant increase in tumor implant growth compared with the vehicle. At the end of histamine administration, the interferon (IFN)-gamma / interleukin (IL)-4 ratio in peripheral lymphocytes, as well as histamine and cytokine levels in tumor implants were determined. Histamine levels in tumor implants remained unchanged after exogenous histamine delivery. Mice with tumor implants exhibited significantly elevated IFN-gamma / IL-4 ratios compared with mice lacking tumors. Nonetheless, the increased IFN-gamma / IL-4 ratios were markedly suppressed by histamine administration compared with vehicle. In addition, histamine delivery significantly decreased IFN-gamma and IL-12 mRNA expression, but increased IL-10 mRNA expression in tumor implants. It was concluded that exogenous histamine dysregulates the balance between T-helper 1 (Th1) and T-helper 2 (Th2) cells, attenuating anti-tumor cytokine expression in the tumor microenvironment, thus resulting in stimulated colorectal cancer growth.
...
PMID:Exogenous histamine stimulates colorectal cancer implant growth via immunosuppression in mice. 1565 89

The transcription factor NF-kappa B is constitutively activated in many human cancers, and induces the expression of multiple proteins including antiapoptotic proteins. Recent papers indicate that NF-kappa B activation is inhibited by interleukin (IL)-10. In this study, we investigated the effect of IL-10 plasmid DNA on colon cancer in mice. In vitro study: Colon 26 murine colon adenocarcinoma cells were either treated or untreated with IL-10 for 60 min. The cells were subsequently stimulated with TNF-alpha. In vivo study: to induce a high level of IL-10 in plasma, we transferred the naked plasmid vectors encoding the mouse IL-10 gene into the liver via the intravenous route. To establish tumors, we injected Colon 26 cells into BALB/c mice subcutaneously. In vitro study: a 24-h incubation with TNF-alpha did not affect cell viabilities; however, pretreatment with IL-10 significantly enhanced the level of apoptosis induced by TNF-alpha. Pretreating Colon 26 cells with IL-10 significantly attenuated the TNF-alpha-induced NF-kappa B activation. In vivo study: IL-10 plasmid controlled the growth of subcutaneous tumors. In subcutaneous tumor, NF-kappa B was activated in response to tumor growth. IL-10 plasmid markedly inhibited this activation of NF-kappa B in subcutaneous tumor. IL-10 plasmid induced cancer cell apoptosis linked to the down-regulation of antiapoptotic proteins, and the activation of caspase-3. These results demonstrate that IL-10 plasmid may constitute a new strategy for treating cancer growth.
...
PMID:Interleukin-10 plasmid DNA inhibits subcutaneous tumor growth of Colon 26 adenocarcinoma in mice. 1567 Aug 94

In the current study, we tested the central hypothesis that exposure to Delta-9-tetrahydrocannabinol (Delta9-THC), the major psychoactive component in marijuana, can lead to enhanced growth of tumors that express low to undetectable levels of cannabinoid receptors by specifically suppressing the antitumor immune response. We demonstrated that the human breast cancer cell lines MCF-7 and MDA-MB-231 and the mouse mammary carcinoma 4T1 express low to undetectable levels of cannabinoid receptors, CB1 and CB2, and that these cells are resistant to Delta9-THC-induced cytotoxicity. Furthermore, exposure of mice to Delta9-THC led to significantly elevated 4T1 tumor growth and metastasis due to inhibition of the specific antitumor immune response in vivo. The suppression of the antitumor immune response was mediated primarily through CB2 as opposed to CB1. Furthermore, exposure to Delta9-THC led to increased production of IL-4 and IL-10, suggesting that Delta9-THC exposure may specifically suppress the cell-mediated Th1 response by enhancing Th2-associated cytokines. This possibility was further supported by microarray data demonstrating the up-regulation of a number of Th2-related genes and the down-regulation of a number of Th1-related genes following exposure to Delta9-THC. Finally, injection of anti-IL-4 and anti-IL-10 mAbs led to a partial reversal of the Delta9-THC-induced suppression of the immune response to 4T1. Such findings suggest that marijuana exposure either recreationally or medicinally may increase the susceptibility to and/or incidence of breast cancer as well as other cancers that do not express cannabinoid receptors and are resistant to Delta9-THC-induced apoptosis.
...
PMID:Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. 1574 59

Cancer rates increase sharply with age in both sexes, and the majority of cases of cancer occur in patients over the age of 65 years. However, the incidence and mortality for cancer level off around 85-90 years of age, followed by a plateau, or even a decline in the last decades of life. Therefore, it seems reasonable to conclude that centenarians are endowed with a peculiar resistance to cancer. Tumor progression is a complex process that depends on interactions between tumor and host cells. One aspect of the host response, the inflammatory response, is of particular interest because it includes the release of proinflammatory cytokines, some of which may promote tumor growth and hence influence survival. Data in the literature reviewed in this paper suggest that some kind of solid tumors are affected by regulatory cytokine genotypes. In particular proinflammatory genotypes characterized by a low IL-10 producer or a high IL-6 producer seem to be associated with a worse clinical outcome. On the other hand, recent evidence has linked IL-10 and IL-6 cytokine polymorphisms to longevity. In fact, those individuals who are genetically predisposed to produce high levels of IL-6 have a reduced capacity to reach the extreme limits of human life, whereas the high IL-10-producer genotype is increased among centenarians. This opposite effect of IL-6 and IL-10 common gene polymorphisms in cancer and longevity is intriguing. These data prompt considerations of the role that antagonistic pleiotropy plays in disease and in longevity. Inflammatory genotypes may be both friends and enemies. In fact, they are an important and necessary part of the normal host responses to pathogens, but the overproduction of inflammatory cytokines might cause immune-inflammatory diseases and eventually death. In fact, our immune system has evolved to control pathogens, so proinflammatory responses are likely to be evolutionarily programmed to resist fatal infections, and a high IL-6 or a low IL-10 production is associated with increased resistance to pathogens. However, decreased level of IL-6 or increased level of IL-10 might better control inflammatory responses and cancer development. These conditions might result in an increased chance of long-life survival in an environment with a reduced antigen (i.e., pathogen) load.
...
PMID:Aging, longevity, inflammation, and cancer. 1591 84

The interleukin (IL)-24/melanoma differentiation associated gene-7 (mda-7) is a member of the IL-10 cytokine family. Introduction of the IL-24 gene into a variety of cancer cells suppresses their growth. It has not been shown, however, whether IL-24 can suppress the growth of hepatoma cells. The purpose of this study was to determine whether the mouse (m)IL-24 gene would suppress hepatoma cells in vivo after being delivered via intramuscular electroporation. After mice were given a subcutaneous dorsal injection of ML-1 hepatoma cells, the mIL-24 gene was delivered and suppressed tumor growth. On day 140, 60% of the mIL-24-treated mice (n=10) and 0% (n=10) of the untreated control mice had survived. We also generated a mouse-hepatoma model by injecting ML-1 cells into the spleen, which resulted in tumor metastasis in the liver. Intramuscular electroporation of mIL-24 also inhibited hepatoma-cell growth in the liver. On day 50, 90% of the experimental mice (n=10) and 40% (n=10) of the control mice had survived. Liver tumors in surviving experimental mice were 50% smaller than those in control mice. IL-24 also inhibited tumor vascularization. These results suggest that IL-24 has potential therapeutic value for hepatoma
...
PMID:IL-24 inhibits the growth of hepatoma cells in vivo. 1595 34

In previous studies, we demonstrated an immune suppressive network in non-small cell lung cancer that is due to overexpression of tumor cyclooxygenase 2 (COX-2). In this study, we assessed the vaccination response to tumor challenge following either pharmacological or genetic inhibition of COX-2 in a murine lung cancer model. Treatment of naive mice with the COX-2 inhibitor, SC-58236, skewed splenocytes toward a type 1 cytokine response, inducing IFN-gamma, IL-12, and IFN-gamma-inducible protein 10, whereas the type 2 cytokines IL-4, IL-5, and IL-10 remained unaltered. Fifty percent of mice receiving SC-58236 and an irradiated tumor cell vaccine completely rejected tumors upon challenge. Those mice that did form tumors following challenge demonstrated a reduced tumor growth. In contrast, all mice either vaccinated with irradiated tumor cells alone or receiving SC-58236 alone showed progressive tumor growth. Studies performed in CD4 and CD8 knockout mice revealed a requirement for the CD4 T lymphocyte subset for the complete rejection of tumors. To determine the role of host COX-2 expression on the vaccination responses, studies were performed in COX-2 gene knockout mice. Compared with control littermates, COX-2(-/-) mice showed a significant tumor growth reduction, whereas heterozygous COX-2(-/+) mice had an intermediate tumor growth reduction following vaccination. In vivo depletion of IFN-gamma abrogated the COX-2 inhibitor-mediated enhancement of the vaccination effect. These findings provide a strong rationale for additional evaluation of the capacity of COX-2 inhibitors to enhance vaccination responses against cancer.
...
PMID:Cyclooxygenase 2 inhibition promotes IFN-gamma-dependent enhancement of antitumor responses. 1600 78

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