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)

Establishment of host-protective memory T cells against tumors is the objective of an antitumor immunoprophylactic strategy such as reinforcing T cell costimulation via CD40-CD40L interaction. Previous CD40-targeted strategies assumed that T cell costimulation is an all-or-none phenomenon. It was unknown whether different levels of CD40L expression induce quantitatively and qualitatively different effector T cell responses. Using mice expressing different levels of CD40L, we demonstrated that the greater the T cell CD40L expression the less tumor growth occurred; the antitumor T cell response was host-protective. Lower levels of CD40L expression on T cells induced IL-10-mediated suppression of tumor-regressing effector CD8(+) T cells and higher productions of IL-4 and IL-10. Using mice expressing different levels of CD40 or by administering different doses of anti-CD40 Ab, similar observations were recorded implying that the induction of protumor or antitumor T cell responses was a function of the extent of CD40 cross-linking. IL-10 neutralization during priming with tumor Ags resulted in a stronger tumor-regressing effector T cell response. Using IL-10(-/-) DC for priming of mice expressing different levels of CD40L and subsequent transfer of the T cells from the primed mice to nu/nu mice, we demonstrated the protumor role of IL-10 in the induction of tumor-promoting T cells. Our results demonstrate that a dose-dependent cross-linking of a costimulatory molecule dictates the functional phenotype of the elicited effector T cell response. The T cell costimulation is a continuum of a function that induces not only graded T cell responses but also two counteracting responses at two extremes.
 ...
PMID:Differential CD40/CD40L expression results in counteracting antitumor immune responses. 1727 8

Many immune therapeutic strategies are under development for melanoma to treat metastatic disease and prevent disease reoccurrence. However, human melanoma cells are often deficient in antigen processing and this appears to play a role in their expansion and escape from immunosurveillance. For example, expression of the transporters associated with antigen processing (TAP1 and TAP2) is down-regulated in the mouse melanoma cell line B16F10. This results in a lack of tumor-associated antigen processing, low surface expression of MHC Class I molecules and low immunogenicity. We observe that restoration of TAP1 expression by transfection resurrects the processing and presentation of viral antigens, and the melanoma-associated antigen, TRP-2. Immunization with irradiated B16F10/rTAP1 transfected cells generates CTLs that are capable of killing B16F10/rTAP1 transfected targets and B16F10 targets deficient in TAP1. Furthermore, B16F10/rTAP1 transfectants grow at a significantly slower rate in mice than B16F10 cells. In an experimental model that closely recapitulates the clinical situation, treatment of B16F10 tumors in mice with a vaccinia virus vector expressing TAP1 also significantly decreases tumor growth in vivo. Furthermore, tumors treated with vaccinia TAP1 had significantly reduced numbers of immunosuppressive, CD3(+)/IL-10 positive, tumor infiltrating lymphocytes. Therefore, TAP1 expression restores both antigen presentation and immunogenicity in B16F10 melanoma cells and concomitantly reduces immunosuppressive IL-10 production at the local tumor site, thereby increasing immunosurveillance mechanisms against tumors.
 ...
PMID:TAP expression reduces IL-10 expressing tumor infiltrating lymphocytes and restores immunosurveillance against melanoma. 1727 2

We have addressed the hypothesis that pathogen-associated immunomodulatory molecules may influence anti-tumor immunity through their pro- and anti-inflammatory activities and abilities to induce effector and regulatory T (Treg) cells. We found that CpG oligonucleotides (CpG) and cholera toxin (CT), which promote Th1 or Th2/Treg cell biased responses, respectively, had differential effects on tumor growth. Therapeutic peritumoral administration of CpG significantly reduced subcutaneous tumor growth and prolonged survival, whereas CT enhanced tumor growth and reduced survival. Peritumoral administration of CpG enhanced the frequency of IFN-gamma-secreting and reduced IL-10-secreting CD4(+) and CD8(+) T cells, in the tumor and in the draining lymph nodes, whereas, CT significantly enhanced the frequency of CD4(+)CD25(+)Foxp3(+) Treg cells, but reduced IFN-gamma-secreting T cells infiltrating the tumor. In contrast to the beneficial effect of CpG in mice with subcutaneous tumors, CpG or CT had no protective effect against tumor growth in the lungs when given therapeutically by the nasal route. However, prophylactic intranasal administration of CpG significantly reduced the number of lung metastases and this was associated with an enhanced frequency of IFN-gamma-secreting CD8(+) T cells in the draining lymph node and enhanced tumor-specific CTL responses. Our findings demonstrate that pathogen-associated molecules can either inhibit or enhance anti-tumor immunity by selectively promoting the induction of effector or regulatory T cells, and that the environment of the growing tumor influences the protective effect.
 ...
PMID:Reciprocal effects of Th1 and Treg cell inducing pathogen-associated immunomodulatory molecules on anti-tumor immunity. 1727 12

The role of cytokines in modulating the formation of new tumors is mediated by their ability to regulate antigen-specific anti-tumor responses and by the activation of non-specific mechanisms, including those involved in the processes of inflammation and innate resistance. Cytokines may influence the growth of tumors by acting directly on tumor cells as growth promoting or growth inhibiting factors or indirectly by attracting inflammatory cell types and affecting angiogenesis. Due to the potency and complexity of cytokine activity against tumor growth, the improvement of cloning techniques and the availability of recombinant forms of different cytokines, a great effort has been made in the recent years to exploit this anti-tumor potential for cancer therapy. This important goal has been difficult to achieve in most cases due to toxicity of most cytokines which could not be dissociated from their anti-tumoral functions. Nevertheless, if well designed, treatment protocols and/or modifications of the cytokine molecules may in some situations augment the anti-tumor effects while limiting the toxicity. One of these molecular approaches could be the design of peptides containing the functional domain of certain cytokines, exemplified by IT9302, a peptide homologous to the functional domain of IL-10, which has demonstrated to increase tumor NK cell sensitivity.
 ...
PMID:Paradoxical effects of cytokines in tumor immune surveillance and tumor immune escape. 1732 45

Cervical cancer develops from the preneoplastic cervical intraepithelial neoplasia (CIN). Host factors are critical in regulating tumor growth and cytokines, which modulate immunologic control may be of particular importance. The objective of this study was to assess the production of cytokines by peripheral blood mononuclear cells (PBMCs) in Indian women with cancer cervix and CIN. Sixty patients with cancer cervix (including all FIGO stage I-IV), 35 patients with CIN, and 30 healthy controls were enrolled in this study. The human papillomavirus (HPV) 16 and 18 status was determined in all the study groups. The PBMC culture supernatant was collected for cytokine estimations by enzyme-linked immunosorbent assay (interleukin-2 [IL-2], interferon-gamma [IFN-gamma], interleukin-4 [IL-4], and interleukin-10 [IL-10]). IL-2 levels showed a significant decline in high-grade CIN and cancer patients, whereas IFN-gamma levels were decreased only in patients with advanced cancer cervix. An increase in the levels of IL-4 and IL-10 was found in all cancer cervix and CIN grade III patients, as compared to those with early CIN grades and healthy controls. The cytokine ratios decreased significantly (P < 0.001 for all the ratios), when cervical cancer patients were compared with controls and CIN cases. The type 2 and type 1 cytokine levels were significantly correlated (P < 0.000) with HPV status. We conclude that a pronounced shift from type 1 to type 2 cytokine production is associated with more severe disease. These data reinforce the need for detailed analysis of immune dysregulation in CIN and cancer cervix patients.
 ...
PMID:Cytokine profile in Indian women with cervical intraepithelial neoplasia and cancer cervix. 1734 6

Procathepsin D (pCD) is a major secreted protein in estrogen receptor-positive (ER+) breast cancer cell lines. Several independent studies have documented pronounced mitogenic effect of secreted pCD on cancer tissue-derived cell lines, including those from breast, lung, and prostate cancer. It has also been shown that the proliferative effect of pCD involves both autocrine and paracrine modes of action. Recent studies have suggested that pCD could act as a key paracrine communicator between cancer and stromal cells. We have shown earlier that the proliferative activity of pCD depends on the activation peptide sequence of pCD. The present study casts light on the mechanism by which pCD influences the proliferation of cancer cells expressing the ER. Results described in the current paper clearly show that pCD initiates secretion of cytokines interleukin-4 (IL-4), IL-8, IL-10, IL-13, macrophage inflammatory protein-1beta and (MIP-1beta) from such tumor cells. Secreted cytokines take part in the proliferation of the cancer cells, as proven by selective inhibition using antibodies. In addition, expression of cytokine receptors on tested cell lines corresponded to the effects of individual cytokines. An analogous pattern was also observed for fibroblasts, which, under physiologic conditions, are the cells in closest contact with the tumor tissue and play a role in tumor growth and invasion. Our observations were further supported by coculture experiments that are in agreement. Although very similar in response to addition of pCD, the invasive ER- cells do not secrete cytokines. Together with previous in vivo results, these data point to pCD as one of key molecules for therapeutic attack in breast cancer.
 ...
PMID:Secretion of cytokines in breast cancer cells: the molecular mechanism of procathepsin D proliferative effects. 1734 17

Injection of dendritic cells (DC) pulsed with tumor antigens is a novel treatment strategy against malignancies, and aims to elicit anti-tumoral cell-mediated immune responses. We studied the in vitro proliferative responses and cytokine production in T cell cultures after 2 stimulations with autologous DC loaded with tumor lysates derived from glioblastoma multiforme (GBM) cells in the presence of recombinant interleukin (rIL)-6/rIL-12 in the first, and rIL-2/rIL-7 in the second stimulation. After the second stimulation, T cells were co-cultured with glioblastoma (GBM) cells and tumor growth suppression by T cells was assessed using a MTT assay. Although loaded DC induced a significant shift towards T helper cell type 1 (Th1) cytokine production as compared to unloaded DC, persistent interleukin (IL)-10 production by T cells both at the end of 2 stimulations with loaded DC and during the effector phase was also required for their tumor suppressive activity. A stronger glioma growth suppressive activity by T cells stimulated with tumor lysate-loaded DC than by control T cells, cultured with unloaded DC, was seen only if the relative IL-10 production after two stimulations with loaded DC was at least 40% of the IL-10 production after two stimulations with unloaded DC. If less than 40% IL-10 was produced in the experimental condition compared to the control condition, T cells also lost their tumor growth suppressive activity. Addition of rIL-10 during stimulation increased the suppressive activity on tumor cell viability and interferon (IFN)-gamma production by T cells that showed Th1 response upon stimulation with loaded DC. The data point towards the production of both IFN-gamma and IL-10 by responding effector T cells, and towards an immune modulatory rather than immune suppressive role of IL-10 to generate anti-tumoral effector T cells against GBM.
 ...
PMID:Persistent IL-10 production is required for glioma growth suppressive activity by Th1-directed effector cells after stimulation with tumor lysate-loaded dendritic cells. 1736 30

Cytokines produced by tumor cells may have various effects on antitumor immune responses and tumor growth. In the present study, the cytokine production of 31 lung cancer cell lines was evaluated, while any correlation with the histological type, the induction of tumor-specific cytotoxic T lymphocytes (CTL) in vitro, and angiogenesis and the infiltration of inflammatory cells in tumor tissues were also examined. Production of interleukin (IL)-1alpha, IL-1beta, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, granulocyte macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor, transforming growth factor (TGF)-beta and vascular endothelial growth factor (VEGF) in the culture supernatant was measured using enzyme-linked immunosorbent assay. Each cytokine was produced in a substantial number of the tumor cell lines. In particular, IL-6, IL-8, TGF-beta and VEGF were produced in 18 (55%), 29 (94%), 31 (100%) and 28 (90%) of 31 cell lines, respectively. However, neither IL-4 nor TNF-alpha was produced at all by any tumor cell line. TGF-beta production was significantly higher in adenocarcinoma than in squamous cell carcinoma (P = 0.03). Immunohistochemical staining revealed the magnitude of macrophage infiltration, and angiogenesis in surgically resected tumor tissue specimens correlated well with GM-CSF and IL-8 production from the corresponding cell lines. Among six lung cancer cell lines, CTL were induced in the three lung cancer cell lines that produced a lower amount of TGF-beta (<100 pg/mL). These findings suggested that TGF-beta produced by tumor cells could inhibit the induction of CTL in vitro. The present results suggest that the production of various cytokines from tumor cells might exert various paracrine effects both in vivo and in vitro.
 ...
PMID:Cytokine production of lung cancer cell lines: Correlation between their production and the inflammatory/immunological responses both in vivo and in vitro. 1751 73

The objective of the current study was to characterize the systemic and local innate immune response of dairy cows to IMI with Mycoplasma bovis, a pathogen of growing concern to the dairy industry. Ten Holstein cows were each infused in 1 quarter with M. bovis and studied for a 10-d period. Acute phase protein synthesis, which reflects 1 parameter of the systemic response to infection, was induced within 108 h of infection, as evidenced by increased circulating concentrations of lipopolysaccharide binding protein and serum amyloid A. Transient neutropenia was observed from 84 to 168 h postinfection, whereas a constant state of lymphopenia and thrombocytopenia was observed from 84 h until the end of the study. Milk somatic cell counts initially increased within 66 h of M. bovis infusion and remained elevated, relative to control (time 0) concentrations, for the remainder of study. Increased milk concentrations of BSA, which reflect increased permeability of the mammary epithelial-endothelial barrier, were evident within 78 h of infection and were sustained from 90 h until the end of the study. Milk concentrations of several cytokines, including IFN-gamma, IL-1beta, IL-10, IL-12, tumor growth factor-alpha, and tumor necrosis factor-alpha, were elevated in response to infection over a period of several days, whereas increases in milk IL-8 were of a more limited duration. Complement activation, reflected by increased milk concentrations of complement factor 5a, was also observed over several days. Despite the indication by these observed changes that the cows mounted a prolonged inflammatory response to M. bovis intramammary infection, all quarters remained infected throughout the study with persistently high concentrations of this bacterium. Thus, a sustained inflammatory response is not sufficient to eradicate M. bovis from the mammary gland and may reflect the ongoing struggle of the host to clear this persistent pathogen.
 ...
PMID:Innate immune response to intramammary Mycoplasma bovis infection. 1758 19

The recently cloned human gene named "placental immunoregulatory ferritin" (PLIF) is a pregnancy-related immunomodulator. Recombinant PLIF and its bioactive domain C48 are immune-suppressive and induce pronounced IL-10 production by immune cells. PLIF is expressed in the placenta and breast cancer cells. Blocking PLIF in pregnant mice by anti-C48 antibodies inhibited placental and fetal growth and modulated the cytokine network. It has been revealed that anti-C48 treatment inhibited MCF-7 tumor growth in nude mice. However, this significant effect was observed only in those transfused with human peripheral blood mononuclear cells. Blocking PLIF in tumor-engrafted human immune cell transfused mice resulted in massive infiltration of human CD45+ cells (mainly CD8+ T cells), both intratumorally and in the tumor periphery, and a significant number of caspase-3+ cells. In vitro, anti-C48 treatment of MCF-7 tumor cells cocultured with human lymphocytes induced a significant increase in interferon-gamma secretion. We conclude that blocking PLIF inhibits breast cancer growth, possibly by an effect on the cytokine network in immune cells and on breakdown of immunosuppression.
 ...
PMID:Antibodies to placental immunoregulatory ferritin with transfer of polyclonal lymphocytes arrest MCF-7 human breast cancer growth in a nude mouse model. 1760 31


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