Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour necrosis factor-alpha (TNF-alpha) is a monocyte (MO)-derived cytokine that plays an essential role in the immunological system. In the present study our aim was to evaluate the levels of TNF-alpha secreted by MO from cancer patients. Blood MO were obtained from 10 lung cancer patients (LCP), 10 colorectal cancer patients (CCP) and 10 healthy donors (HD). TNF-alpha levels in MO culture supernatants spontaneously (sp) secreted or after stimulation with LPS treatment were evaluated using a commercial ELISA kit (sensibility: 10-1000 pg/ml). Mean values, expressed as pg/ml were: LCP: sp= 452.6+/-107.2, LPS= 589.5+/-126.7); CCP: sp= 84.1+/-25.0, LPS= 437.3+/-93.2; HD: sp= 74.2+/-21.5, LPS= 573.5+/-87.1. We concluded that MO from LCP secrete high levels of TNF-alpha spontaneously (p< 0.003 versus HD) and it was also observed an absence of response to LPS treatment in the 33% of the cases in these patients.
 ...
PMID:Tumor necrosis factor-alfa production by monocytes from lung and colorectal cancer patients. 1137 Aug 33

TK5048 and its derivatives, AM-132, AM-138, and AM-97, are recently developed antimitotic (AM) compounds. These 1-phenylpropenone derivatives induce cell cycle arrest at the G2 / M phase of the cell cycle. TK5048 inhibited tubulin polymerization in human lung cancer PC-14 cells in a concentration-dependent manner. In a polymerization assay using bovine brain tubulin, AM-132 and AM-138 were quite strong, AM-97 was moderately strong, and TK5048 was a relatively weak inhibitor of tubulin polymerization. A murine leukemia cell line resistant to a sulfonamide antimitotic agent, E7010, which binds to colchicine-binding sites on tubulin, was cross-resistant to the in vitro growth-inhibitory effect of AM compounds. Inhibition of tubulin polymerization is therefore one of the mechanisms of action of these AM compounds against tumor cells. To profile the antitumor effect of AM compounds, the in vivo antitumor effect of AM-132 was evaluated against cytokine-secreting Lewis lung carcinoma (LLC). Tumor-bearing mice were treated with intravenous AM-132 using three different treatment schedules. LLC tumors expressing tumor necrosis factor-alpha (TNF-alpha), granulocyte macrophage colony-stimulating factor (GM-CSF), or interleukin (IL)-6 were very sensitive to AM-132. In particular, LLC tumors expressing IL-6 were markedly reduced by AM-132 treatment, and showed coloring of the tumor surface and unusual hemorrhagic necrosis. These results suggest a combined effect of AM-132 and cytokines on the blood supply to tumors.
 ...
PMID:Enhancement of in vivo antitumor activity of a novel antimitotic 1-phenylpropenone derivative, AM-132, by tumor necrosis factor-alpha or interleukin-6. 1147 28

Elevated VEGF blood concentrations have been proven to be associated with poor prognosis in human neoplasms. This finding is generally explained as a consequence of the potential angiogenic properties of VEGF itself. However, preliminary experimental studies suggest that VEGF, in addition to its angiogenic activity, may also play an immunosuppressant role by inhibiting dendritic cell (DC) maturation. The present study was performed to analyze blood levels of VEGF in cancer patients in relation to those of another potentially angiogenic tumor growth factor, endothelin-1 (ET-1), and to the absolute number of circulating immature and mature DC, and serum levels of the best known antitumor cytokine, IL-12. The study was performed in 100 healthy controls and in 80 solid tumor patients (colorectal cancer: 24; gastric cancer: 17; cancer of pancreas: 4; lung cancer: 13; breast cancer: 11; renal cell cancer: 6; gynecologic tumors: 5), 48 of whom showed distant organ metastases. In each patient, we have evaluated serum concentrations of VEGF-165, total VEGF, ET-1, IL-12 and the circulating number of immature (CD123+) and mature (CD11c+) DC. Mean serum levels of VEGF-165 were significantly higher in metastatic patients than in controls or in non-metastatic patients, whereas the total amounts of VEGF were not significantly higher. Moreover, it has been observed that patients with abnormally elevated blood concentrations of VEGF-165 showed significantly lower mean values of immature DC, mature DC and IL-12 and significantly higher mean levels of ET-1 than those with normal concentrations. This study, by confirming that advanced neoplastic disease may be associated with increased endogenous secretion of VEGF, seems to suggest that the association between high blood levels of VEGF and poor prognosis in cancer does not depend only on VEGF-induced stimulation of the neovascularization, but also on VEGF-related immunosuppression.
 ...
PMID:Abnormally enhanced blood concentrations of vascular endothelial growth factor (VEGF) in metastatic cancer patients and their relation to circulating dendritic cells, IL-12 and endothelin-1. 1150 71

The identification of circulating tumor antigens or their related autoantibodies provides a means for early cancer diagnosis as well as leads for therapy. The purpose of this study was to identify proteins that commonly induce a humoral response in lung cancer by using a proteomic approach and to investigate biological processes that may be associated with the development of autoantibodies. Aliquots of solubilized proteins from a lung adenocarcinoma cell line (A549) and from lung tumors were subjected to two-dimensional PAGE, followed by Western blot analysis in which individual sera were tested for primary antibodies. Sera from 54 newly diagnosed patients with lung cancer and 60 patients with other cancers and from 61 noncancer controls were analyzed. Sera from 60% of patients with lung adenocarcinoma and 33% of patients with squamous cell lung carcinoma but none of the noncancer controls exhibited IgG-based reactivity against proteins identified as glycosylated annexins I and/or II. Immunohistochemical analysis showed that annexin I was expressed diffusely in neoplastic cells in lung tumor tissues, whereas annexin II was predominant at the cell surface. Interestingly, IL-6 levels were significantly higher in sera of antibody-positive lung cancer patients compared with antibody-negative patients and controls. We conclude that an immune response manifested by annexins I and II autoantibodies occurs commonly in lung cancer and is associated with high circulating levels of an inflammatory cytokine. The proteomic approach we have implemented has utility for the development of serum-based assays for cancer diagnosis as we report in this paper on the discovery of antiannexins I and/or II in sera from patients with lung cancer.
 ...
PMID:An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer. 1150 47

Nitric oxide (NO) is synthesized in the lung and this free radical participates in a wide array of regulatory, protective, and adverse interactions with cells. Both excess NO and its insufficiency have been implicated in the pathogenesis of numerous lung diseases with inflammatory components. Much of the available data concerning the source and regulation of NO production is derived from rodent systems. However, the requirements for NO production are more stringent in human monocytes/macrophages than in rodent systems. In contrast to rodent macrophages, human moncytes/macrophages generally do not respond to cytokine triggers with NO production [J. Leukocyte Biol. 58 (1995) 643, J. Exp. Med. 181 (1995) 735] and if NO is detected the levels are generally low [J. Leukocyte Biol. 58 (1995) 643]. The regulation of macrophage NO in the human appears to be a more selective and variable process than that seen in the rodent macrophages. In the human lung, the function of NO as toxic pro-inflammatory or protective anti-inflammatory agent is unresolved. While not a major source of NO in the human lung, the alveolar macrophage is an important producer of cytokines and this production may be modified by NO. Clear evidence of abnormalities in NO levels in the lungs of patients with asthma, bronchiectasis, viral infections, lung cancer and primary pulmonary hypertension (PPH) has been documented. Elevated inflammatory cytokines and oxidant production have been associated with all of these disease states. In terms of cytokine production, NO has been shown to decrease nuclear factor kappa B (NF-kappaB) activation. However, oxidants may interact with NO to form toxic compounds (e.g., NO combines with superoxide anion to form peroxynitrite). Furthermore, such reactions may decrease the availability of NO for blocking inflammatory cytokine production. Thus, available data suggests that a multiplicity of factors affect NO regulatory properties in inflammatory situations.
 ...
PMID:Human alveolar macrophages and monocytes as a source and target for nitric oxide. 1151 13

An in vitro assay system was developed to assess the potency of the human innate immune system by measurement of IL-12, IL-18, IL-10 and IFNgamma in the supernatants of bacillus Calmette-Guerin cell wall skeleton (BCG-CWS)-stimulated blood samples. BCG-CWS is a ligand for Toll-like receptor (TLR) 2 and 4, and activates monocytes to macrophages (Mphi), and immature dendritic cells to mature antigen-presenting cells (APC). This system was found to allow the discrimination of immune suppressive states in patients with lung cancer from normal immune states in light of the cytokine profile. The following results were deduced from analyses of BCG-CWS-stimulated blood samples of lung cancer patients with reference to normal subjects. (1) The levels of production of IFNgamma and IL-10 by lymphocytes were decreased. (2) IL-12 p40 production by monocytes/Mphi was upregulated, while that of IL-10 was downregulated. (3) IL-18 was detected in all patients in a range similar to normal subjects. (4) Responses of lymphocytes to IL-2 and IL- 18 in terms of IFNgamma production were diminished. (5) The upregulated IL-12 levels were recovered to within the normal range in most patients after tumor resection. (6) Male patients showed more severe suppression of IL-12/IL-18-mediated IFNgamma production than female patients. Thus, the lesser IFNgamma production observed in patients' blood with high IL-12 p40 levels in response to BCG-CWS may reflect the production of p40 dimers or IL-23 instead of p70, or the presence of some unknown pathways to prohibit the interface between the innate and acquired immune systems. BCG-CWS-mediated Toll signaling may participate in IFNgamma induction for lymphocytes through Mphi/APC IL-12/I-18 modulation.
 ...
PMID:Interferon gamma-producing ability in blood lymphocytes of patients with lung cancer through activation of the innate immune system by BCG cell wall skeleton. 1151 19

The antitumor efficiency of secondary lymphoid organ chemokine (SLC), a CC chemokine that chemoattracts both dendritic cells (DCs) and T lymphocytes,was evaluated in SV40 large T-antigen transgenic mice that develop bilateral multifocal pulmonary adenocarcinomas. Injection of recombinant SLC in the axillary lymph node region led to a marked reduction in tumor burden with extensive lymphocytic and DC infiltration of the tumors and enhanced survival. SLC injection led to significant increases in CD4 and CD8 lymphocytes as well as DC at the tumor sites, lymph nodes, and spleen. The cellular infiltrates were accompanied by the enhanced elaboration of Type 1 cytokines and the antiangiogenic chemokines IFN-gamma inducible protein 10, and monokine induced by IFN-gamma (MIG). In contrast, lymph node and tumor site production of the immunosuppressive cytokine transforming growth factor beta was decreased in response to SLC treatment. In vitro, after stimulation with irradiated autologous tumor, splenocytes from SLC-treated mice secreted significantly more IFN-gamma and granulocyte macrophage colony-stimulating factor, but reduced levels of interleukin 10. Significant reduction in tumor burden in a model in which tumors develop in an organ-specific manner provides a strong rationale for additional evaluation of SLC in regulation of tumor immunity and its use in lung cancer immunotherapy.
 ...
PMID:Secondary lymphoid organ chemokine reduces pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma. 1152 34

A panel of 31 long-term non-small cell lung cancer (NSCLC) cell lines was examined for the expression of protein and/or mRNA transcripts for 11 distinct immune response related molecules or tumor associated antigens (TAA). To assess whether cytokine stimulation might up-regulate expression of the genes of interest, cells were cultured in 500 U/ml of gamma-interferon (gamma-IFN) for 48-72 h prior to analysis. Major histocompatibility complex (MHC) Class I antigens were detected by indirect immunofluorescence and were constitutively expressed on all of the cell lines. The average of the mean fluorescence intensity (MFI) measured 222+/-22. gamma-IFN stimulation produced a significant increase to 482+/-36. For MHC Class II only 7/31 cell lines (23%) exhibited constitutive expression, while gamma-IFN treatment had a dramatic effect and yielded 18/31 (58%) positive cell lines. The co-stimulatory molecules CD80 and CD86 were examined by direct immunofluorescence for cell surface expression and RT-PCR amplification for mRNA. CD80 protein was not detected at all, while an insignificant percentage of cells were positive (mean 2%) for CD86 in all cell lines tested. gamma-IFN had no apparent effect on CD80 or CD86 protein expression. Constitutive CD80 or CD86 mRNA levels were observed in 45 and 61% of the NSCLC lines, respectively. These percentages increased to 77% and 90% with gamma-IFN. Cell surface phenotypic analysis for TAA revealed positive populations in 28/31 cell lines (90%) for Her-2/neu, 18/31 (58%) for CEA and 8/31 (26%) for GD-2, with gamma-IFN having no effect. After gamma-IFN stimulation, RT-PCR amplification for Mage-1, -2, -3 and WT-1 detected mRNA in 33%, 33%, 44% and 70% of the cell lines, respectively. Overall, gamma-IFN stimulation led to the up-regulation of MHC Class I molecules and class II molecules as well as CD80 and CD86 mRNA transcripts. This survey represents the first comprehensive analysis of NSCLC cell lines for a variety of molecules that could play an important role in the generation of an NSCLC anti-tumor CD8+ cytotoxic T lymphocyte (CTL) response.
Lung Cancer
PMID:Characterization of human non-small cell lung cancer (NSCLC) cell lines for expression of MHC, co-stimulatory molecules and tumor-associated antigens. 1155 13

Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that increases microvascular permeability and directly stimulates endothelial cell growth and angiogenesis. Recent evidence suggests that the genetic regulation of angiogenesis is also of crucial importance and that oncogenes and tumor suppressor genes can regulate it. The aim of this study was to determine the prognostic value of VEGF and its possible association with p53-gene mutation in 89 stage I-IIIa surgically treated NSCLC patients. DNA sequencing of the p53 gene (exons 5-8) showed 40 mutations (45%). Among the 89 NSCLC patients, immunoreactivity for VEGF was weakly, moderately and strongly positive in 35 (39%),36 (40%) and 18 (20%) cases, respectively. A strong, statistically significant association was found between the presence of a p53 gene mutation and expression of VEGF (P<0.001). The positive result of the p53 mutation increased the odds of observing a higher level of VEGF expression approximately 9.5 times (95% confidence interval: [3.44,25.89]). In the univariate analysis of survival, increasing levels of VEGF expression were associated with poor prognosis (P<0.001 for trend). In the multivariate analysis, after adjusting for the presence of a p53-gene mutation, gender, TNM stage and histological type, the prognostic effect of VEGF expression level was marginally non-significant (P=0.077). When the two-category quantification of the VEGF level was considered (low vs. intermediate/high), a marginally significant (P=0.024), unfavorable effect of intermediate/high levels of VEGF expression, independent of the effect of the presence of a p53-gene mutation, was found. In conclusion, we found that the p53 mutation was closely related to VEGF expression. Additionally, we observed that an intermediate/high expression of VEGF might be a useful indicator of prognosis in NSCLC. This latter conjecture, suggested by an analysis of the data, ought however, to be independently verified in further studies.
Lung Cancer 2001 Dec
PMID:Expression of vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC): association with p53 gene mutation and prognosis. 1172 Jul 43

Heparanase activity is correlated with the metastatic potential of several cancer cells and is a key enzyme in the breakdown of tissue barriers. It is also involved in the regulation of growth factor and cytokine activity. However, little is known about the factors that induce heparanase in cancer cells. We investigated the effect of three growth factors, platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF), on heparanase mRNA induction in lung cancer cells in vitro. In addition, we examined the effect of erythromycin (EM) and clarithromycin (CAM), which are 14-membered ring macrolide antibiotics that act as biological response modifiers, on the expression of heparanase mRNA induced by growth factors. PDGF, HGF and bFGF stimulated cell migration activity and enhanced the expression of heparanase mRNA in the human lung adenocarcinoma cell line A549. Via different mechanisms, EM and CAM modulate the induction by these factors of heparanase mRNA expression on A549 cells. EM also significantly suppressed A549 cell migration induced by PDGF and HGF, and CAM significantly suppressed A549cell migration induced by bFGF. The results suggest that the growth factors PDGF, HGF and bFGF are important inducers of heparanase in potentially invasive and metastatic cancer cells. The suppressive effect of heparanase mRNA expression by EM and CAM may have interestingtherapeutic applications in the prevention of metastasis.
 ...
PMID:Erythromycin and clarithromycin modulation of growth factor-induced expression of heparanase mRNA on human lung cancer cells in vitro. 1175 10


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