UMLS:C0178874 - FACTA Search

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Query: UMLS:C0178874 (tumor progression)
40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

According to recent advances in psychoneuroimmunology concerning the neurobiochemistry of emotions, the pshychological status of cancer patients should be investigated in relation to the function of the psychoneurodocrine system, in an attempt to put into evidence possible cancer progression-related alterations, particularly those involving the dopaminergic pathways, which play a fundamental role in the perception of pleasure. In fact, the decreased capacity of feeling pleasure is one of the most frequent psychic symptoms occurring in cancer patients. Rorschach's test has been proven to be an appropriate psychological tool to investigate psychic condition including sexual and spiritual profiles. On this basis, a study was planned to evaluate if a relation exists between psychological response to Rorschach's test and immunoneuroendocrine status of cancer patients. The immune status was investigated by measuring lymphocyte subsets and serum levels of IL-2 and IL-10. The neuroendocrine status was analyzed by evaluating the endocrine response of PRL, GH and cortisol to an oral administration of apomorphine (0.01 mg/kg b.w.), a dopaminergic agent able to explore dopaminergic sensitivity. The study included 40 cancer patients (breast cancer: 15; colorectal cancer: 14; lung cancer: 11), 21 of whom showed distant organ metastases. Rorschach's test demonstrated a simultaneous suppression of sexual and spiritual profiles in 31/40 (78%) patients, without significant differences in relation to either tumor histotype or disease state. A normal decline in PRL levels and a normal increase in those of GH and cortisol was observed in 29/40 (73%), 5/40 (13%) and 9/40 (23%) patients. The percent of normal responses of PRL, GH and cortisol was higher in patients with normal than in those with altered response to Rorschach's test, even though only the difference in PRL and cortisol response was statistically significant. Patients with normal sexual and spiritual expression at Rorschach's test showed a significantly higher number of total lymphocytes, T lymphocytes, T helper lymphocytes and NK cells with respect to the patients with altered psychological response, whereas no difference was found in T cytotoxic lymphocyte mean number. IL-2 and IL-10 mean serum concentrations were lower and higher, respectively, in patients with altered than in those with normal response to Rorschach's test, even though only the difference in IL-10 values was statitistically significant. This preliminary study, carried out to analyze the psychological status of cancer patients in relation to neuroendocrine and immune conditions, would suggest that neoplastic disease is characterized by a simultaneous suppression of sexual and spiritual profiles, and that this is associated with neuroendocrine alterations and immunosuppression.
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PMID:A psychoncological study of lymphocyte subpopulations in relation to pleasure-related neurobiochemistry and sexual and spiritual profile to Rorschach's test in early or advanced cancer patients. 1506 61

Effector T cells fall into two subpopulations based on cytokine-secretion. Type 1 cells secrete IFN-gamma, whereas type 2 cells secrete IL-4, IL-10, and GM-CSF. NKT cells represent a third subpopulation that secretes similar cytokines and have been associated with immunoregulation. Using the TS/A adenocarcinoma, we assessed the phenotype and kinetics of tumor-infiltrating lymphocytes (TIL) in mice challenged subcutaneously in the mammary region. Flow cytometric analysis shows that T cells do not infiltrate the primary tumor site until days 7-14 following tumor challenge. Both CD4 and CD8 TILs were predominantly CD44(High) and expressed CD25, CD69, and CD95 cell surface activation markers. Activated CD4/CD44(High) TIL numbers reached peak levels at day 21 that precipitously decreased by day 28 whereas corresponding CD8 cell numbers progressively increased, however, at lower levels and with later kinetics. Intracellular cytokine staining showed that greater numbers of IL-4-producing Th2 cells were elicited and with earlier kinetics than that of IFN-gamma-producing Th1 cells. T cells co-expressing DX5 (CD3(+)/DX5(+)) emerged (>21 days), suggesting a recruitment of NK-like T cells at later stages of tumor progression. Moreover, tumors selectively up-regulated TGF-beta, MIF, and IP-10 gene expression at times as early as day 4, with peak levels at day 7 in vivo. Such gene expression remained elevated and correlated with a continued progression in tumor growth suggesting that preferential effector cell recruitment and production of select factors during different stages of tumor maturation may aid in regulating effective endogenous antitumor responses in progressive breast cancer.
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PMID:Type 1 and type 2 tumor infiltrating effector cell subpopulations in progressive breast cancer. 1509 54

Nitric oxide (NO*) synthesis is induced within many tumors. The timecourse of NO* synthesis was evaluated during intraperitoneal Meth A fibrosarcoma progression. While increasing macrophage recruitment into ascites was noted, inducible nitric oxide synthase (iNOS) antigen and function peaked between days 3-6 after tumor implantation. The capacity of cells to respond to LPS and IFNgamma stimulation was markedly depressed on day 9 and 11. Cellular proliferation correlated in an inverse fashion with levels of NO* synthesis. Electron paramagnetic resonance spectroscopy and nitrotyrosine immunostaining failed to show accumulation of characteristic target cell lesions induced by NO*. These findings lead us to conclude that NO* production was increasingly suppressed during Meth A tumor progression. Depression of NO* production did not correlate with levels of the inhibitory cytokines TGFbeta and IL-10, but could be partially overcome by addition of sepiapterin (a tetrahydrobiopterin prodrug). Thus, depletion of essential co-factors necessary for iNOS function may contribute to depressed NO* responses during cancer progression.
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PMID:Suppression of cytokine-inducible nitric oxide synthesis during intraperitoneal meth a tumor growth. 1519 99

Nitric oxide (NO*) synthesis is induced within many tumors. The time course of NO* synthesis was evaluated during intra-peritoneal Meth A fibrosarcoma progression. While increasing macrophage recruitment into ascites was noted, inducible nitric oxide synthase (iNOS) antigen and function peaked between days 3-6 after tumor implantation. The capacity of cells to respond to LPS and IFNgamma stimulation was markedly depressed on day 9 and 11. Cellular proliferation correlated in an inverse fashion with levels of NO* synthesis. Electron paramagnetic resonance spectroscopy and nitrotyrosine immunostaining failed to show accumulation of characteristic target cell lesions induced by NO*. These findings lead us to conclude that NO* production was increasingly suppressed during Meth A tumor progression. Depression of NO* production did not correlate with levels of the inhibitory cytokines TGFbeta and IL-10, but could be partially overcome by addition of sepiapterin (a tetrahydrobiopterin prodrug). Thus, depletion of essential co-factors necessary for iNOS function may contribute to depressed NO* responses during cancer progression.
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PMID:Suppression of cytokine-inducible nitric oxide synthesis during intraperitoneal Meth A tumor growth. 1513 64

Increased levels of interleukin (IL)-10 have been described as a negative prognostic indicator for survival in patients with various types of cancer. IL-10 exerts tolerogenic and immunosuppressive effects on dendritic cells, which are crucial for the induction of an antitumor immune response. Blood dendritic cell antigen (BDCA)-2 and BDCA-4 are specifically expressed by CD123(bright) CD11c- plasmacytoid dendritic cells; whereas BDCA-1 and BDCA-3 define 2 distinct subsets of CD11c+ myeloid dendritic cells. In this study, the T-helper cell (Th)1/Th2 cytokine serum profile of 65 hepatocellular carcinoma patients was assessed. We found that serum levels of IL-10 were substantially increased in hepatocellular carcinoma patients as compared with controls. Peripheral blood mononuclear cells from healthy volunteers were exposed to recombinant human (rh)IL-10 in vitro to additionally characterize its impact on distinct blood dendritic cell subsets. A dramatic decrease of all myeloid dendritic cell (MDC) and plasmacytoid dendritic cell (PDC) subsets was detectable after 24 hours of continuous rhIL-10 exposure. Moreover, the expression of HLA-DR, CD80 and CD86, was significantly reduced on rhIL-10-treated dendritic cell subsets. Direct ex vivo flow cytometric analysis of various dendritic cell subpopulations in peripheral blood from hepatocellular carcinoma patients revealed an immature phenotype and a substantial reduction of circulating dendritic cells that was associated with increased IL-10 concentrations in serum and with tumor progression. These findings confirm a predominantly immunosuppressive role of IL-10 for circulating dendritic cells in patients with hepatocellular carcinoma and, thus, may indicate novel aspects of tumor immune evasion.
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PMID:Increased levels of interleukin-10 in serum from patients with hepatocellular carcinoma correlate with profound numerical deficiencies and immature phenotype of circulating dendritic cell subsets. 1553

Tumor environment can be critical for preventing the immunological destruction of antigenic tumors. We have observed a selective accumulation of CD4(+)CD25(+) T cells inside tumors. In a murine fibrosarcoma L(d)-expressing Ag104, these cells made up the majority of tumor-infiltrating lymphocytes at the late stage of tumor progression, and their depletion during the effector phase, rather than priming phase, successfully enhanced antitumor immunity. We show here that CD4(+)CD25(+) T cells suppressed the proliferation and interferon-gamma production of CD8(+) T cells in vivo at the local tumor site. Blockade of the effects of IL-10 and TGF-beta partially reversed the suppression imposed by the CD4(+) cells. Furthermore, local depletion of CD4(+) cells inside the tumor resulted in a change of cytokine milieu and led to the eradication of well-established highly aggressive tumors and the development of long-term antitumor memory. Therefore, CD4(+)CD25(+) T cells maintained an environment in the tumor that concealed the immunogenicity of tumor cells to permit progressive growth of antigenic tumors. Our study illustrates that the suppression of antitumor immunity by regulatory T cells occurs predominantly at the tumor site, and that local reversal of suppression, even at a late stage of tumor development, can be an effective treatment for well-established cancers.
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PMID:Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. 1575 11

The predominance of type two cytokines in syngeneic B16 tumor-bearing mice was confirmed by analysing supernatant contents and mRNA copies of IFN-gamma, IL-4, IL-5, IL-10 and IL-13 from splenocytes. The cytokine-producing lymphocytes were then examined by double-staining flowcytometry. Both CD4+IFN-gamma+ T cells and DX5+IFN-gamma+ NK cells from spleen significantly declined, interestingly, the declining degrees of DX5+IFN-gamma+ NK cells were much greater than those of CD4+IFN-gamma+ T cells by the percentage in whole NK or T cells or the absolute amounts per spleen at early tumor stage (day 10) or tumor-advanced stage (day 20). In contrast to DX5+IFN-gamma+ NK cells, DX5+IL-10+ NK cells increased during tumor progression, the increasing degrees of DX5+IL-10+ NK cells were also much greater than those of CD4+IL-10+ T cells by the percentage or the absolute amounts. Though the percentage of DX5+IL-4+ NK cells only increased in early tumor stage (day 10), the increasing degree was also greater than that of CD4+IL-4+ T cells. In 20xfield view under laser confocal microscope, the mean numbers of DX5+IFN-gamma+ NK cells and CD4+IFN-gamma+ T cells dramatically declined after tumor inoculation. These results suggest that cytokines produced by NK cells, at least partly, account for the balance of type one and two cytokines as done by T cells, and in some conditions, that the NK1 or NK2 cells were possibly more sensitive to tumor progression.
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PMID:Tumor-induced suppression of interferon-gamma production and enhancement of interleukin-10 production by natural killer (NK) cells: paralleled to CD4+ T cells. 1582 92

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.
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PMID:Aging, longevity, inflammation, and cancer. 1591 84

Hepatocyte growth factor (HGF) plays an important role in many biological events such as angiogenesis, cell proliferation, anti-fibrosis and antiapoptosis. It is well known that HGF promotes tumor progression and suppresses development of fibrosis after tissue injury. In contrast, its role in immune-mediated disorders has not been fully clarified. In the present study, we examined the role of HGF in Ag-specific immune response using in vitro studies and an experimental model of allergic airway inflammation. We first confirmed that dendritic cells (DCs) expressed the receptor for HGF, c-met, which was not expressed in T cells. Treatment with HGF both in vitro and in vivo potently suppressed DC functions such as Ag-presenting capacity, thus down-regulating Ag-induced Th1- and Th2-type immune responses. Exogenous administration of the HGF expression plasmid into Ag-primed mice markedly suppressed the development of airway eosinophilia and airway hyperresponsiveness, which was induced by Ag inhalation, with suppression of the Ag-presenting capacity of DCs in the lung. HGF exhibited these immunosuppressive effects without up-regulation of IL-10 or TGF-beta. We also found that expression of endogenous HGF in the lung significantly increased following Ag sensitization and inhalation challenges. Finally, neutralization of endogenous HGF in vivo significantly increased airway eosinophilia and airway hyperresponsiveness with up-regulation of the Ag-presenting capacity of DCs in the lung. These results demonstrated a novel, significant, and possibly therapeutic role of HGF as a potent regulator in immune-mediated disorders such as asthma.
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PMID:A novel role of hepatocyte growth factor as an immune regulator through suppressing dendritic cell function. 1617 22

Apoptotic cells can be eliminated by phagocytosis, which is mediated by antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs), through phosphatidylserine (PS) on apoptotic cells and phosphatidylserine receptor (PSR) on APCs. The phagocytosis of apoptotic cells by macrophages is strictly regulated by not only the inflammatory reaction, but also by an increase in anti-inflammatory factors such as IL-10, TGF-beta, and prostaglandin E2 (PGE2), leading to an anti-inflammatory situation, whereby apoptosis contributes to a noninflammatory response. However, because PS and PSR are expressed in cancer cells, shed soluble phosphatidylserine (sPS) can interact with the PS receptor on macrophages, which promotes an anti-inflammatory response to macrophages that may lead to immune escape. The sPS derived from cancer cells also reacts with the PSR on the cancer cells to produce IL-10, TGF-beta, and PGE2, which can cause suppression of anti-tumor immunity through the anti-inflammatory response to macrophages, which produces tumor-associated macrophages. Furthermore, sPS and TGF-beta inhibit the maturation of immature DCs, resulting in a functional inhibition of DCs. The potential roles of PS and PSR in cancer cells and macrophages in immune escape mediated by sPS and anti-inflammatory factors are discussed, which may explain their dual regulation of anti- and pro-inflammatory responses during tumor progression.
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PMID:Cancer cell immune escape and tumor progression by exploitation of anti-inflammatory and pro-inflammatory responses. 1617 62

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