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)

Progression of cervical cancer is associated with excessive circulating levels of cytokines, which are known to be modulators of tumor angiogenesis. The concentrations of cytokines and growth factors were assayed using enzyme-linked immunosorbant assays in the serum of 61 women in various stages of cancer [stage 0 (n = 6), stage I (n = 15), stage II (n = 15), stage III (n = 15), and stage IV (n = 10)] and of 20 healthy control subjects. Our results indicated that b-FGF and TNF-beta levels were significantly elevated in stage I, and serum levels of TGF-beta and IL-7 were elevated in stages II-IV of invasive carcinoma. Our experimental subjects had significantly increased serum levels of IL-6, GM-CSF, and angiogenin in stages I-IV of cervical cancer, and TNF-alpha serum levels were elevated in all stages of invasive carcinoma. The serum levels of IL-8 and IL-10 were elevated only in stages II-III, and the levels of IL-2 were elevated in stages III-IV. The serum levels of IL-1 alpha and IL-1 beta remained unaltered in all stages of cancer progression. Progression of cervical cancer is associated with increased serum levels of angiogenin, IL-2, IL-6, IL-7, IL-8, IL-10, b-FGF TNF-alpha, TGF-beta, TNF-beta, and GM-CSF during different stages, all of which have the potential to be angiogenic amplifiers.
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PMID:Circulating serum levels of cytokines and angiogenic factors in patients with cervical cancer. 954 28

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

Human interleukin-6 (hIL-6) acts as a growth factor in several human B lymphoid cancers. As human herpesvirus-8 (HHV-8) encodes for a viral IL-6 (vIL-6), the viral cytokine may be responsible for several manifestations of HHV-8-related disorders. Using an anti-hIL-6 mAb (B-E8) which does not recognize vIL-6, we investigated the involvement of the human cytokine in the proliferation of HHV-8-positive primary effusion lymphoma (PEL) cells. In vitro, 5/5 PEL cell lines produced hIL-6 (4 to 1,200 pg/ml). The EBV- HHV-8+ cell line (BCBL-1) was adapted to grow in SCID mice. hIL-6 was detected in the serum of mice with grafts, as well as human soluble CD138 (sCD138) and human IL-10 (hIL-10). The serum level of these mediators increased with tumor progression. The effect of treatment with the B-E8 mAb on the tumor progression and survival was evaluated. This treatment significantly slowed down the tumor development: on day 54, there were more mice with low levels of sCD138 and hIL-10 in the treated group than in controls (p = 0.03 and 0.02, respectively); treatment also delayed death (median date of death was day 65 for control mice and day 84 for anti-hIL-6 mAb-treated mice; p < 0.02). Thus, hIL-6 is expressed in addition to vIL-6 in HHV-8-positive malignant B lymphocytes, and the viral cytokine does not totally substitute for human IL-6 in promoting tumor progression.
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PMID:Human interleukin-6 is in vivo an autocrine growth factor for human herpesvirus-8-infected malignant B lymphocytes. 1058 16

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

Based upon positive immunologic comparisons, protein and cDNA sequencing, and in vitro and in vivo immunogenicity studies we propose that carcinomas, sarcomas and lymphomas/leukemias of rodents and humans share 37 kDa Onco-Fetal Antigen [OFA] as a T and B-lymphocyte stimulating, universal tumor specific transplantation antigen [UTSTA]. In the past four years, biochemical studies from several laboratories studying laminin receptor protein and immunological studies of OFA from our laboratories independently converged. OFA protein and immature or precursor Laminin Receptor Protein [iLRP] are > 99% identical proteins based on amino acid and cDNA sequencing and immunobiology studies summarized here. Acquired expression of 37 kDa OFA/iLRP enables malignant tumor cells to penetrate laminin tissue and vessel barriers. 37 kDa OFA/iLRP activates precursor thymic anti-OFA/iLRP specific cytotoxic T cell which kill emerging pretumor cells. Our reported findings also demonstrate that OFA/iLRP can function to induce specific immunoregulatory CD8 T-suppressor cells secreting IL-10 which impair effector T-cell killing of emerging tumor cells non-specifically and thereby facilitate tumor progression. Potential applications of OFA/iLRP detection in early cancer formation, for monitoring patient T cell subclass responses to OFA/iLRP as a predictor of tumor progression, and the use of OFA/iLRP peptides for specific anti-tumor immunotherapy are presented.
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PMID:37 kiloDalton oncofetal antigen protein and immature laminin receptor protein are identical, universal T-cell inducing immunogens on primary rodent and human cancers. 1069 12

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 cathepsins B, L, and H are expressed ubiquitously and represent the major proportion of lysosomal enzymes. They are involved in bulk proteolysis in the lysosomes, processing of proteins and matrix degradation. Under pathological conditions the participation of cathepsins, especially their secreted forms, was observed in inflammation, tumor progression and metastasis. The enzymatic activity of cathepsins is regulated by posttranslational modification, localization, maturation, changes in pH, and their interaction with inhibitors. Regulation at the level of transcription is not well elucidated. The aim of this study was to investigate the effect of IL-1 beta, IL-6, IL-10, TGF-beta 1, and HGF on mRNA expression and protein level in human lung epithelial cell lines A-549 and BEAS-2B. IL-6 leads to a twofold increase in cathepsin L mRNA expression, whereas TGF-beta 1 decreases the amount of cathepsin L mRNA. At protein level, using enzyme immunoassay, it was shown that IL-6 induced increased amounts of cathepsin L but not cathepsin B. In contrast, after incubation of bronchial epithelial cells with TGF-beta 1 the cathepsin L concentration was decreased. In conclusion, gene expression of cathepsins B and L is variable. The cytokines IL-6 and TGF-beta 1 modulate cathepsin gene expression.
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PMID:Expression of cathepsins B and L in human lung epithelial cells is regulated by cytokines. 1084 56

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

Cathepsins B and L are commonly expressed cysteine proteinases that play a major role in lysosomal bulk proteolysis, protein processing, matrix degradation, and tissue remodeling. Cathepsins are also implicated in tumor progression and metastasis, tissue injury, and inflammation. Cells at sites of inflammation often show upregulation and secretion of cathepsins. The regulation of cathepsin expression by inflammatory mediators is not well understood. The aims of this study were to investigate the effect of the cytokines interleukin-1 beta (IL-1 beta), IL-6, IL-10, transforming growth factor-beta 1 (TGF-beta 1), and hepatocyte growth factor (HGF) on expression of cathepsin B and cathepsin L mRNA (quantitative RT-PCR), on protein expression (ELISA, Western blot), and also on enzymatic activity of cathepsins B and L. Investigations were performed using the human lung epithelial cell line A-549. IL-6 was found to induce a concentration-dependent increase in mRNA expression, protein concentration, and enzymatic activity of cathepsin L. Cathepsin B mRNA and protein expression were not affected by IL-6. In contrast, TGF-beta 1 decreased the amount of cathepsin L mRNA and cathepsin B mRNA. At protein level, it was shown that TGF-beta 1 clearly reduced the concentration of cathepsin L but not cathepsin B. The cytokines IL-1 beta, IL-10, and HGF were found to exert no effect on cathepsin B and L expression. In conclusion, these results are the first to show that IL-6 and TGF-beta 1 have opposite effects on the regulation of expression of cathepsins B and L in A-549 human lung epithelial cells. The proinflammatory cytokine IL-6 induced an upregulation of cathepsin L, whereas TGF-beta 1 suppressed cathepsin B and L expression. Further studies are needed to clarify the mechanism that affects cathepsin B and L expression.
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PMID:Interleukin-6 and transforming growth factor-beta 1 control expression of cathepsins B and L in human lung epithelial cells. 1117 76

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