Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 12(IL-12) is a heterodimeric cytokine that has potent anti-tumor and anti-metastatic activities. Although clinical trials of recombinant human IL-12 have begun in patients with several advanced malignancies, very few studies have investigated the preoperative serum levels of IL-12 in patients with gastric or colorectal cancer. The purpose of the present study was to investigate the relationships between the preoperative serum levels of IL-12 and clinicopathological factors in patients with gastric or colorectal cancer. Blood was obtained before surgery from 14 patients with gastric cancer and 15 patients with colorectal cancer. Serum levels of IL-12 was assessed using the quantitative sandwich enzyme immunoassay technique. Although not statistically significantly, low serum levels of IL-12 tended to be associated with gastric cancer patients who were node-positive, CEA positive, had tumors that penetrated the serosa, had tumors greater than 5 cm in diameter, were more than 60 years-old, or were more advanced than stage IIIA(TNM) or stage IIIa(Japanese Research Society for Gastric Cancer). Patients with colorectal cancer who were node-positive, had tumors that penetrated the serosa, were more than 60 years-old, or were more advanced than stage III(TNM), stage IIIa(Japanese Society for Cancer of the Colon and Rectum) and Dukes' C also tended to have low serum IL-12 levels. These results suggest that low serum levels of IL-12 may be observed in more advanced gastric and colorectal cancer patients. Thus, patients with low serum levels of IL-12 in gastric or colorectal cancer may require additional immunochemotherapy after surgery.
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PMID:Serum levels of interleukin-12 in patients with gastrointestinal cancer. 1076 8

Hepatocyte growth factor (HGF) is a stromal cell-derived cytokine that can stimulate invasion and metastasis of carcinoma cells. Recent studies have shown that the serum HGF concentration is elevated in patients with gastric cancer and may be a useful disease marker. However, the origin of the elevated serum HGF remains undetermined. We investigated the site of HGF production by analyzing the relationships between the HGF expression in tumor tissues, the serum HGF concentrations and inflammation in patients with gastric cancer. The serum and tissue HGF concentrations were measured by an enzyme-linked immunosorbent assay. The serum HGF concentration was higher than the normal cut-off level (0.57 ng/ml) in 44% of the patients. Surgical removal of the tumor significantly reduced the serum HGF concentration, suggesting that the tumor tissue was responsible for the increase. Western blotting analysis showed that the HGF protein was expressed in 20 out of 22 tumor tissues. The concentration of HGF in the tumor tissue was significantly higher than that in normal gastric mucosa. Significant correlation was found between tissue HGF concentrations and serum HGF concentrations. No significant correlation was found between the serum HGF concentration and white blood cell count or C-reactive protein concentration, indicating that the increase in serum HGF is not due to inflammation related to the tumor. These results suggest that the elevated serum HGF concentration in patients with gastric cancer is mediated by production from the tumor tissue.
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PMID:Elevation of serum hepatocyte growth factor concentration in patients with gastric cancer is mediated by production from tumor tissue. 1081 Apr 32

The complete genome sequence revealed a family of 32 outer membrane proteins (OMPs) in Helicobacter pylori. We examined the effect of four OMPs (HP0638, HP0796, HP1501, and babA2) on the production of the proinflammatory cytokine, IL-8. Mutants of the four OMPs, as well as cagE and galE from H. pylori from the U.S. and Japan, were constructed by inserting a chloramphenicol-resistant cassette into the gene. Twenty-two pairs of parental and mutant H. pylori strains, as well as 160 clinical isolates (80 from Japanese and 80 from U.S.), were cocultured with gastric cancer cell lines. IL-8 production in the supernatant and adhesion was assayed by ELISA. HP0796, HP1501, babA2, and galE gene knockouts had no significant effect on IL-8 production. Knockout of the HP0638 gene in 81% of cag-positive strains reduced IL-8 production approximately 50%. The three cag-positive strains in which IL-8 levels were unchanged by HP0638 knockout had five or seven CT dinucleotide repeats in the 5' region, resulting in a frame shift and truncation. Strains with naturally inactive HP0638 gene were all from the U.S.; Japanese strains were always "on" and thus, on average, may be more virulent. Although cag-negative isolates produced a limited IL-8 response, cag-negative strains that contained a functional HP0638 gene produced more than 3-fold greater IL-8 than cag-negative nonfunctional HP0638 strains. We hypothesize that functional HP0638 gene may be an important virulence factor in relation to the risk of clinically significant outcomes of H. pylori infection. We denote HP0638 gene as outer inflammatory protein (oipA).
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PMID:A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. 1085 59

Helicobacter pylori is a gram-negative bacterium that resides under microaerobic conditions in a neutral microenvironment between the mucus and the superficial epithelium of the stomach. From this site, it stimulates cytokine production by epithelial cells that recruit and activate immune and inflammatory cells in the underlying lamina propria, causing chronic, active gastritis. Although epidemiological evidence shows that infection generally occurs in children, the inflammatory changes progress throughout life. H. pylori has also been recognized as a pathogen that causes gastroduodenal ulcers and gastric cancer. These more severe manifestations of the infection usually occur later in life and in a minority of infected subjects. To intervene and protect those who might be at greatest risk of the more severe disease outcomes, it is of great interest to determine whether bacterial, host, or environmental factors can be used to predict these events. To date, several epidemiological studies have attempted to define the factors affecting the transmission of H. pylori and the expression of gastroduodenal disease caused by this infection. Many other laboratories have focused on identifying bacterial factors that explain the variable expression of clinical disease associated with this infection. An alternative hypothesis is that microorganisms that cause lifelong infections can ill afford to express virulence factors that directly cause disease, because the risk of losing the host is too great. Rather, we propose that gastroduodenal disease associated with H. pylori infection is predominantly a result of inappropriately regulated gastric immune responses to the infection. In this model, the interactions between the immune/inflammatory response, gastric physiology, and host repair mechanisms would dictate the disease outcome in response to infection.
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PMID:The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer. 1101 39

It has been established that cancer patients have immunosuppressive substances in their sera that depress cellular immunity. Although plasma exchanges have been attempted to remove these substances and to improve immunity to cancer, little is known about its mechanism from the viewpoint of cytokine pattern. The levels of the cytokines, tumour necrosis factor-alpha, interleukin 1beta, interleukin 6, interferon-gamma and interleukin-1 receptor antagonist (IL-1ra) by peripheral blood mononuclear cells (PBMC) were determined simultaneously by the whole-blood assay and the PBMC assay in 20 patients with gastric cancer and in 10 healthy volunteers. In both assays the cytokine levels were lower in patients with cancer compared with healthy controls, with the exception of IL-1ra. In the PBMC assay, the IL-1ra level in cancer patients was significantly higher than that in controls. No statistical correlation between the cytokine levels determined by the two assays was found. We suggest that autologous serum deprivation restored and enhanced IL-1ra production, and normalized the cytokine cascade in immune response, in patients with gastric cancer.
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PMID:Autologous serum deprivation restored IL-1 receptor antagonist production by peripheral blood mononuclear cells in patients with gastric cancer. 1119 21

To evaluate the mechanisms of T-cell dysfunction in patients with gastric cancer, we investigated the caspase activity of T cells, the induction of spontaneous T-cell apoptosis, the expression of T-cell receptor (TCR) zeta molecules, and the ability of T cells to produce cytokines in peripheral blood lymphocytes from patients (n = 22) and healthy controls (n = 14). The caspase-3 activity of T cells was studied as the protease activity of caspase-3 using the cell-permeable substrate of PhiPhiLux G1D2. Flow cytometric analysis was performed with triple staining by annexin V-FITC, propidium iodide, and CD3-R-phycoerythrin-Cy5 for the detection of T-cell apoptosis and with intracellular staining using permeabilized cells for the expression of TCR-zeta molecules. IFN-gamma and tumor necrosis factor alpha production from T cells was evaluated in response to anti-CD3 stimulation. Caspase-3 activity of peripheral blood T cells from patients with advanced disease was significantly increased compared with that from controls [15.5 +/- 3.6 mean fluorescence intensity (MFI) versus 11.5 +/- 3.3 MFI; P = 0.0068]. Parallel to this, the apoptosis of peripheral blood T cells from patients with advanced disease was significantly higher than for those from controls (16.5 +/- 15.5% versus 4.8 +/- 2.7%; P = 0.010). Furthermore, the expression of TCR-zeta molecules in patients with advanced disease was significantly decreased in comparison with that of the controls (41.0 +/- 13.9 MFI versus 56.7 +/- 16.3 MFI; P = 0.014), and this decreased expression coexisted with impaired IFN-gamma (42.4 +/- 43.2 pg/ml versus 1,757.4 +/- 2449.0 pg/ml; P = 0.031) and tumor necrosis factor alpha (682.6 +/- 519.3 pg/ml versus 1,686.0 +/- 1,533.7 pg/ml; P = 0.041) production of T cells. Thus, peripheral blood T cells from gastric cancer patients simultaneously exhibit an elevated caspase-3 activity, an increased degree of T-cell apoptosis, a down-regulation of TCR-zeta molecules, and impaired cytokine production. These observations suggest that induction of T-cell apoptosis coexisting with a down-regulation of TCR-zeta molecules may be responsible for T-cell dysfunction in patients with gastric cancer.
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PMID:Elevated caspase-3 activity in peripheral blood T cells coexists with increased degree of T-cell apoptosis and down-regulation of TCR zeta molecules in patients with gastric cancer. 1120 21

Cutaneous metastatic diseases remain nearly incurable and a major medical challenge. It has been shown that interleukin-2 (IL-2) has potential as a therapeutic agent for various neoplastic diseases such as melanoma, renal cell carcinoma and myeloid leukaemia. However, IL-2 therapy for metastatic skin lesions has not been established yet. In the present study, we investigated the effect of recombinant IL-2 in a 79-year-old Japanese man with carcinoma erysipeloides, a rare type of cutaneous metastasis from gastric cancer. He was treated with an intralesional injection of rIL-2 (200 000 JRU) daily. Ten days after treatment, an erythematous plaque was eliminated almost completely leaving light brown pigmentation. A skin biopsy from the pigmented area revealed the absence of obvious tumour cells. These findings suggest that this cytokine should be considered for the clinical treatment of several inoperative metastatic cutaneous diseases, including gastric cancer.
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PMID:Regressive effect of intralesional injection of a moderate dose of recombinant interleukin-2 on carcinoma erysipeloides from gastric carcinoma. 1126 Jan 77

Allogeneic transfusion seems to drive the immune system toward a Th2 response and away from a Th1 response, providing a hypothetical mechanism for transfusion-induced immunomodulation. By means of an intracytoplasmic cytokine detection technique with flow cytometry, it is possible to measure Th1 and Th2 cells derived from peripheral blood mononuclear cells. This study evaluated the presence of transfusion-induced immunomodulation in 11 gastric cancer patients after gastrectomy with perioperative blood transfusion, compared to 11 gastric cancer patients who were treated by gastrectomy without transfusion. Lymphocytes subsets, including CD4 T cells, CD8 T cells, CD4/CD8 Ratio, CD2(+) T cells, CD3(+) T cells, and CD19(+) B cells, were measured in these patients, as well as variables that might suggest transfusion-induced immunomodulation, such as duration of antibiotic use, duration of hospital stay, and total hospital charges. This study also measured changes in the Th1/Th2 ratio. Th1 and Th2 lymphocytes were characterized by measuring intracellular expression of cytokines with flow cytometry. Cells were stimulated with phorbol myristate acetate and ionomycin in the presence of brefeldin-A. The results showed no significant differences in lymphocyte subsets, Th1/Th2 ratio, total hospital charges, or duration of antibiotic utilization between the groups of transfused and non-transfused gastric cancer patients after gastrectomy. The only significant difference was a longer hospital stay for transfused patients (mean 20.5 da) compared to non-transfused patients (mean 16.2 da). The anticipated finding of a Th2 response after blood transfusion was not observed. A larger group of patients may be needed to document such an effect, since many confounding variables affect the morbidity and outcome of surgery in these patients.
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PMID:Search for immunomodulatory effects of blood transfusion in gastric cancer patients: flow cytometry of Th1/Th2 cells in peripheral blood. 1133 7

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.
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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 cytotoxin-associated gene (cagA) and vacuolating cytotoxin (Vac) production have been reported to be major virulence factors of Helicobacter pylori. However, there have been some disputes regarding the correlation between these virulence factors and clinical outcomes. We evaluated whether the cagA-positive genotype and Vac production might be correlated with various gastroduodenal diseases in Korea and whether this correlation could be due to differences in proinflammatory cytokine gene expression and apoptosis of gastric epithelial cells in vitro. The presence of the cagA gene was examined by the polymerase chain reaction (PCR), and Vac production was detected using the bacterial culture supernatant and HeLa cells after H. pylori was isolated from Korean patients. Gastric epithelial cells were infected with cagA+Vac+, cagA+Vac-, or cagA-Vac- strains, after which cytokine gene expression was evaluated, using quantitative reverse transcription (RT)-PCR. Apoptosis and caspase-3 activation were measured in H. pylori-infected gastric epithelial cells. There was no significant correlation between the presence of these virulence factors in H. pylori isolates and peptic ulcer or gastric cancer. Upregulation of cytokine gene expression, including that of interleukin (IL)-1alpha, IL-8, granulocyte macrophage colony-stimulating factor (GM-CSF), and monocyte chemotactic protein (MCP)-1, as well as apoptosis and caspase-3 activation, were similar in infections with cagA-positive and cagA-negative strains, but were not correlated with the production of Vac. These results suggest that the lack of correlation between virulence factors of isolated H. pylori strains and serious gastroduodenal disease entities in Korea may be due to the similar capacity for proinflammatory cytokine gene expression and apoptosis caused by infection with each of the H. pylori strains.
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PMID:Virulence factors of Helicobacter pylori in Korean isolates do not influence proinflammatory cytokine gene expression and apoptosis in human gastric epithelial cells, nor do these factors influence the clinical outcome. 1157 34


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