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

The effect of a panel of cytokines on the proliferation and type IV collagenase production was studied in four melanoma cell lines of different origin, tumorigenicity and metastatic capacity. TGF-b, TNF-a and to a lesser extent, IL-1a exhibited antiproliferative effect on the cell lines, with some lines showing varying degree of resistance. The sensitivity did not correlate directly with the origin or the biological behavior of the tumor lines, suggesting that cytokine resistance of advanced stage melanoma cells may be relative. IL-2, IL-10 and IL-12 displayed little or no effect on proliferation. The effect of cytokines on metalloproteinase production showed a cell line dependent pattern. Interestingly, those cytokines that exhibited the most pronounced antiproliferative activity, also proved most effective in stimulating collagenase secretion, often simultaneously, in the same line. The results indicate that pleiotropic cytokines can have positive and negative effects simultaneously on various steps of tumor progression.
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PMID:Cytokine sensitivity of metastatic human melanoma cell lines-- simultaneous inhibition of proliferation and enhancement of gelatinase activity. 965 95

IFN-gamma production in whole blood cell cultures (WBCC), and TNF-receptor p75 (TNF-R-75) plasma levels were measured as two independent immunological parameters in a group of 67 untreated renal cell carcinoma (RCC) patients at different clinical stages, and 40 age matched healthy controls. In the blood cell cultures of the tumor patients the levels of IFN-gamma were significantly lower compared to the controls and the values decreased with increasing tumor mass. In contrast, TNF-R-75 plasma levels were significantly higher in the tumor patients and increased with tumor stage. Additionally serial assessments of these parameters were studied in another group of 15 patients with advanced RCC during treatment with IL-2, IFN-alpha and retinoic acid according to three different protocols in order to search for any correlation between the biological marker values and the clinical response to treatment. During each 5 day cycle of high dose IL-2/IFN-alpha combination therapy (protocol 1) IFN-gamma-levels in the WBCC were markedly decreased, whereas the plasma levels of TNF-R-75 were increased. During low dose, long-term continuous IFN-alpha/IL-2 administration (protocol 2) in two patients a clear increase of the ex vivo leukocyte IFN-gamma production was seen for the first 5 and 6 months of treatment, respectively, which could be correlated to stable disease for this time. When progression was diagnosed, IFN-gamma levels in the WBCC decreased. In the WBCC of the other four patients with progressive IFN-gamma levels were rather low throughout (< 10 ng/ml) and no clear changes were measured. During low does IFN-alpha and 13-cis-retinoic acid therapy in repetitive weekly cycles (protocol 3) two patients had stable disease for 6 and 14 months respectively. In the WBCC cultures of these patients IFN-gamma production was higher during stable than during progressive disease. The other two patients with tumor progression had a very low leukocyte IFN-gamma production and high plasma levels of TNF-R-75. It is concluded that IFN-gamma levels in WBCC and TNF-R-75 plasma levels may be useful parameters for the immunological monitoring of therapies with biological response modifiers. Low IFN-gamma values and high TNF-R-75 levels may be predictive of tumor progression and bad prognosis.
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PMID:Correlation of clinical and immunological parameters of metastatic renal cell carcinoma patients undergoing therapy with interleukin 2, interferon-alpha and retinoic acid. 967 39

Recently there has been considerable conjecture in the literature concerning a possible relationship between stress, depression and bereavement, and carcinoma. We shall propose a causal model in which the relationship between stress, depression and carcinoma is clarified. This relationship is grounded on dysregulation of the inflammatory cytokines in stress and depression. Stress is associated with increased expression of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), and reduced expression of IL-2, interferon-gamma (IFN-gamma), major histocompatability complex (MHC) class II molecules and natural killer cell activity (NKA). Depression is associated with elevated IFN-gamma and IL-1 beta, downregulated IL-2, and reduced NKA. Most organ-related carcinomas are associated with elevated TNF-alpha, which inhibits the activity of protein tyrosine phosphatase (PTPase), the enzyme that initiates activation of the MHC class I pathway. Sustained elevation of TNF-alpha inhibits the activity of PTPase which results in diminished expression of the MHC class I antigen on the cell surface and thus, malignant cells escape immune surveillance. Therefore, stress and depression can foster tumor progression by means of inhibiting the expression of MHC class I and II molecules and through the reduction of NKA.
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PMID:An immunological model connecting the pathogenesis of stress, depression and carcinoma. 982 37

Cytokines constitute a diverse group of intercellular signaling proteins that regulate local and systemic, immune and inflammatory responses as well as wound healing and hematopoiesis. The proliferation and maturation of cells of the immune system, both normal and malignant, is regulated by cytokines such as the interleukins. Such cytokines may also influence the proliferation and differentiation of other cell types. Prostate epithelial cells differentiate along two pathways, exocrine or neuroendocrine. Elevation in the exocrine marker prostate-specific antigen and/or the neuroendocrine marker chromogranin A in serum has been associated with prostate cancer progression. Interleukin-1 (IL-1) mRNA is expressed by two androgen-insensitive (AI) but not by three androgen-sensitive prostate cancer cell lines. IL-1 inhibits while IL-2 stimulates the growth of the androgen-sensitive LNCaP cell line. Neither affects growth of AI PC-3 or DU-145 cell lines. IL-1 promotes the neuroendocrine phenotype and IL-2 promotes the exocrine phenotype in prostate cancer. The influence of the immune mediators IL-1 and IL-2 on the growth and differentiation of prostate cancer cells and its implication in tumor progression is described herein. Relationship of IL-1 with bone metastasis and the involvement of ss-2 microglobulin in the development and progression of prostate cancer are also discussed.
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PMID:Neuroendocrine and immune mediators in prostate cancer progression. 985 13

IL-2 activated natural killer (A-NK) cells have the capacity to infiltrate metastatic tumors and lyse tumor cells. Nevertheless, adoptive immunotherapy with lymphokine-activated killer cells has been only modestly effective in the clinic and has not routinely provided long-term survival in patients with established cancer metastases. This may indicate the need for more carefully investigating the role of effector cells of the immune response, including A-NK cells, in models of tumor progression. Herein we describe the use of the MMTV/v-Ha-ras transgenic mouse model as a system for exploring the role of NK cells during tumor progression. We have examined the lytic capacity of A-NK cells generated from tumor-free and tumor-bearing transgenic oncomice against standard A-NK cell targets (YAC-1 and P815) in addition to tumor cells isolated from these animals. A-NK cells generated from mice without obvious tumor burden show higher lytic activity than A-NK cells generated from mice with evident tumors, i.e., those at a more advanced stage of tumor progression. Only long term (8-day) cultures of late passage A-NK cells generated from tumor-bearing mice showed significant increases in lytic activity over those generated from tumor-free mice. These results suggest that experimental protocols using transgenic oncomice at various stages of tumor growth may constitute a novel model for testing the role of A-NK cells for their capacity to interfere with cancer progression.
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PMID:Cytolytic activities of IL-2 activated NK cells from MMTV/v-Ha-ras transgenic oncomice during tumor progression. 989 Dec 21

We have previously reported that transfection of mouse interferon gamma (IFN-gamma) in H-2Kk-positive BW variants (BW-Sp3) abolishes tumorigenicity and reduces metastatic capacity. To further increase the immunogenicity of BW-Sp3 cells, the gene for human interleukin 2 (huIL-2) was transfected in these cancer cells. Single BW-Sp3(huIL-2) and double BW-Sp3(huIL-2+IFN-gamma) transfectants were generated and their behavior was investigated as compared to parental and IFN-gamma-transfected BW-Sp3. Although expression of huIL-2 was equally effective as IFN-gamma in preventing tumor formation and reducing experimental metastasis, it did not confer protection to spontaneous metastases and even reversed the anti-metastatic activity of IFN-gamma. Inoculation of the BW variants in immunocompromised mice revealed that expression of IL-2 activates both T cells and aspecific immune effectors. However, in immunocompromised mice a clear pro-metastatic effect of IL-2 was recorded. Analysis of membrane antigens on the different variants showed a selective effect of huIL-2 on the expression of two surface antigens, i.e. L-selectin and metastatic T cell hybridoma antigen (MTH), which may contribute to metastasis. Hence upon expression of huIL-2 in T lymphoma variants, tumor outcome will depend on the balanced effects of the transfected cytokines on the immune response and the redirected effect on tumor progression.
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PMID:Multiple effects of transfection with interleukin 2 and/or interferon gamma on the behavior of mouse T lymphoma cells. 1009 40

Physiologically, B-lymphocytes are not present in the skin. Even in pathological situations they rarely occur. In contrast, primary cutaneous B-cell lymphomas (CBCL) are characterized by proliferation of B lymphocytes within the skin. This suggests the existence of a certain microenvironment supporting homing and expansion of clonal B cells. Cytokines were demonstrated to be involved in the pathogenesis of cutaneous lymphomas of T-cell origin. Cytokine expression in cutaneous B-cell lymphoma lesions, however, has not been investigated so far. Therefore, the mRNA level of several cytokines was analyzed in biopsies from 7 patients with CBCL and compared to pleomorphic T-cell lymphoma (n = 6), psoriasis (n = 9), and healthy skin (n = 7), using a competitive RT-PCR approach. An overexpression of TNF-alpha, IL-10, and IL-6 was found. Enhanced IL-8 mRNA expression was detected in 2/7 cases. The overexpression of IL-6 and IL-10 in CBCL might be of particular importance, since these cytokines are considered to support B-cell growth. Additionally, the overexpression of IL-10 may contribute to tumor progression since this immunosuppressive cytokine might be involved in downregulation of immunological tumor surveillance, in part by inhibiting type 1 cytokine formation. In fact, we did not detect IFN-gamma and IL-2 expression. Taken together, we found a cytokine pattern in CBCL lesions which might contribute to tumor B-cell growth.
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PMID:Cytokine expression in primary cutaneous germinal center cell lymphomas. 1068 78

The aim of this study was to examine the tolerability, antitumor activity, and biological effects of a new schedule of i.v. recombinant human interleukin 12 (rhIL-12). Twenty-eight patients were enrolled in a Phase I trial in which rhIL-12 was administered twice weekly as an i.v. bolus for 6 weeks. Stable or responding patients were eligible to receive additional 6-week cycles until there was no evidence of disease or until tumor progression. Patient cohorts were treated with escalating doses of rhIL-12 (30-700 ng/kg). The maximum tolerated dose (MTD) was 500 ng/kg, with dose-limiting toxicities consisting of elevated hepatic transaminases and cytopenias. At the MTD (n = 14), there was one partial response occurring after 6 cycles of rhIL-12 in a patient with renal cell cancer. Two additional renal cell cancer patients treated at the MTD had prolonged disease stabilization, with one of these exhibiting tumor regression after 8 cycles of rhIL-12. IFN-gamma, IL-15, and IL-18 were induced in patients treated with rhIL-12. Whereas IFN-gamma and IL-15 induction were attenuated midway through the first cycle in patients with disease progression, those patients with tumor regression or prolonged disease stabilization were able to maintain IFN-gamma, IL-15, and IL-18 induction. The down-modulation of IFN-gamma induction during rhIL-12 treatment did not relate to IL-10 production or alterations in rhIL-12 bioavailability but was associated with an acquired defect in lymphocyte IFN-gamma production in response to IL-12, IL-2, or IL-15. This defect could be partially overcome in vitro through combined stimulation with IL-12 plus IL-2. These findings show that the chronic administration of twice-weekly i.v. rhIL-12 is well-tolerated, stimulates the production of IL-12 costimulatory cytokines and IFN-gamma, and can induce delayed tumor regression. Strategies aimed at maintaining IFN-gamma induction, such as the addition of IL-2, may further augment the response rate to this schedule of rhIL-12.
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PMID:Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response. 1081 86

The soluble form of carcinoembryonic antigen (sCEA), an oncofetal glycoprotein, is frequently produced by human epithelial-tumor cells, particularly of colorectal origin, and evaluated as a prognostic index of tumor progression and patient survival. sCEA molecules are often present at high concentrations in the peripheral blood of colorectal cancer patients, but the function and significance of this are not well understood. Reported data have demonstrated that sCEA can interfere in NK-cell/tumor-cell interaction by drastically reducing the lysis of tumor cells in a dose-dependent manner and can also suppress T and B cell functions. The aim of our study was to evaluate this situation in colorectal cancer by determining peripheral blood immunological parameters in a group of patients and healthy subjects. We evaluated the interleukin (IL)-2, interferon (IFN) gamma, IL-4, sIL-2R and IL-10 levels in the serum and the release of IFN gamma, IL-4 and IL-10 from peripheral blood mononuclear cells (PBMC); the PBMC expression of CD3, CD16 and CD19 phenotypic antigens; the PBMC proliferative responses to IL-2, IL-2 + anti-CD3 monoclonal antibody (mCD3) and mCD3. The statistical evaluation of our overall results strongly indicates that the high level of the sCEA molecules in the patient's serum might act as a suppressive factor for NK and TH1 immunocompetent cells. This may be the cause of sCEA involvement in tumor progression, and indicates the possibility of an improvement in cancer treatment through its manipulation.
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PMID:The sCEA molecule suppressive role in NK and TH1 cell functions in colorectal cancer. 1085 73

The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for the early detection of disease. Adenomas have been identified as precursors of colorectal cancer and tumor establishment, and disease progression has been found to reflect a malfunction of the immune system. We previously indicated the investigation of cytokine serum levels in these patients as a useful and non-invasive tool for the study of the disease progression and an imbalance at TH1 and TH2 cell levels was also found. Moreover, the soluble form of interleukin (IL) 2 receptor (sIL-2R) level is an in vivo marker of T cell activation and is used to monitor the activation of the immune system. We therefore performed an immunological study on a group of healthy subjects, subjects with adenomas, and colorectal cancer patients to identify peripheral blood invasiveness markers in the progression from normal mucosa through adenoma to tumor. In this paper we evaluated the relationships between serum levels of interleukin IL-2, sIL-2R, interferon (IFN) gamma, IL-4, IL-6, IL-10 and sICAM-1 and their networks. Our overall data indicate that in the normal mucosa through adenoma to tumor progression, the host immune response proceeded from a TH1 cell-mediated immune response type (healthy subjects) to a type with TH2 suppressive characteristics (adenoma subjects and cancer patients). However, in the adenoma subjects there was no IL-10 or sIL-2R involvement, while these parameters were implicated in the cancer patients' immune responses. Moreover, a concurrent augmentation of sIL-2R and IL-10 levels seems to be prognostic for the passage from adenoma to cancer, and the sIL-2R and sICAM-1 molecules appear to be involved in the invasiveness mechanisms.
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PMID:IL-10 and sIL-2R serum levels as possible peripheral blood prognostic markers in the passage from adenoma to colorectal cancer. 1085 74


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