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D Basso

Publications and source records attributed to D Basso.

At least 37 records · Page 2Linked to original sources
PubMed2000

Interleukin-6 blood level is associated with circulating carcinoembryonic antigen and prognosis in patients with colorectal cancer.

BACKGROUND: Interleukin-6 (IL-6) is an important proinflammatory cytokine that has multiple effects on stimulating inflammation and cell growth. Experimental data suggest that carcinoembryonic antigen (CEA) induces the systemic production of IL-6 and that IL-6 may stimulate tumor cell growth at metastatic sites. We tested the hypothesis that blood concentrations of IL-6 are associated with the amount of circulating CEA and with prognosis in patients with colorectal cancer. METHODS: CEA and IL-6 concentrations were measured by using enzyme immunoassay in preoperative serum samples from 208 patients with stages I through IV colorectal cancer. RESULTS: Linear regression analysis showed a significant association between serum values of CEA and IL-6 (r = .544; R2 = .296; P < .001). Patients with stage III and stage IV disease had a significantly higher IL-6 serum concentration than those with stage I and stage II disease. In patients with stages I through III, 5-year survival was 83% in cases with concentrations of IL-6 at 10 pg/ml or less (n = 94) and 56% in cases with IL-6 concentrations of more than 10 pg/ml (n = 54; P = .001; median follow-up time, 46 months). By using multivariate analysis, an IL-6 concentration of more than 10 pg/ml was an independent prognostic factor of survival (relative risk = 1.820; P = .020). CONCLUSIONS: In patients with colorectal cancer, blood concentration of IL-6 is associated with high circulating CEA and advanced stage. Furthermore, an IL-6 concentration of more than 10 pg/ml is an independent negative prognostic marker of survival.

Adult↗
PubMed2000

ME-PCR for the identification of mutated K-ras in serum and bile of pancreatic cancer patients: an unsatisfactory technique for clinical applications.

Our aim was to assess the clinical reliability of mutated K-ras detection in serum or bile for the diagnosis of pancreatic cancer using ME-PCR. DNA was extracted from 1 ml serum obtained from 29 patients with pancreatic cancer and 12 control subjects. ME-PCR was optimized using a mixture of normal DNA added with different amounts of mutated DNA. The analysis of sera obtained from the 29 patients and of bile obtained from 11 pancreatic cancer patients demonstrated the presence of mutated K-ras in two (6.9%) and four cases (36%). By contrast K-ras was not amplifiable in any of the 12 serum samples obtained from healthy controls. In conclusion the DNA obtained from pancreatic cancer patients' sera is suitable for K-ras amplification and for the identification of codon 12 point mutations. However ME-PCR alone has an unsatisfactory sensitivity for the detection of pancreatic cancer using serum DNA as starting template.

Adult↗
PubMed2000

Total PSA, free PSA/total PSA ratio, and molecular PSA detection in prostate cancer: which is clinically effective and when?

OBJECTIVES: To ascertain when the serum determination of the free prostate-specific antigen (PSA)/total PSA (fPSA/tPSA) ratio is clinically useful, and whether the identification of PSA or prostate-specific membrane antigen (PSM) mRNA in circulating cells has diagnostic advantages over the determination of their protein product. METHODS: fPSA, tPSA, and the fPSA/tPSA ratio were determined in the sera of 50 men with benign nonprostatic urologic diseases (EPD), 112 patients with prostate cancer (PCa), and 218 with benign prostatic hyperplasia (BPH). mRNA was extracted from the circulating mononuclear cells of 13 EPD samples, 25 PCa samples, and 38 BPH samples. PSA and PSM mRNA signals were identified in these samples by means of reverse transcriptase-polymerase chain reaction. RESULTS: Overall, at a fixed specificity of 95%, the sensitivity of tPSA was 19% and that of the fPSA/tPSA ratio was 40% in distinguishing PCa from BPH. The fPSA/tPSA ratio allowed the discrimination of PCa from BPH with satisfactory sensitivity and specificity when considering patients less than 60 years of age (100% and 95%, respectively). PSA and PSM mRNA were positive in 1 and 7 of 13 EPD samples, 6 and 13 of 25 PCa samples, and 6 and 17 of 38 BPH samples. The Gleason score did not correlate with tPSA, the fPSA/tPSA ratio, PSA mRNA, or PSM mRNA. CONCLUSIONS: The serum determination of the fPSA/tPSA ratio is an excellent index of PCa for subjects younger than 60 years of age; the clinical utility of PSA mRNA identification in circulating cells needs to be validated by large follow-up studies, and the analysis of PSM mRNA seems to be of no clinical interest.

Aged↗
PubMed2000

CEA mRNA identification in peripheral blood is feasible for colorectal, but not for gastric or pancreatic cancer staging.

OBJECTIVE: It has been suggested that the molecular identification of cancer cells in the circulation may be useful in predicting the presence of micrometastasis in several cancer types. The aim of the present study was therefore to assess the feasibility of CEA mRNA identification in blood for diagnosing and staging colorectal, gastric and pancreatic cancer. METHODS: We studied 16 control subjects, 69 patients with colorectal (CRC), 30 with gastric (GC), 27 with pancreatic cancer (PC) and 8 with benign diseases of the pancreatobiliary tree. At diagnosis CEA mRNA was identified in peripheral blood by means of a RT-PCR procedure. RESULTS: The specificity of this test in control subjects was 94%, and its sensitivity in identifying CRC, GC and PC were 34, 37 and 41%, respectively. False-positive findings were recorded in 25% patients with benign diseases. No association was found between CEA mRNA and stage in patients with GC or PC. In CRC patients, positive CEA mRNA findings were correlated with local spread (chi(2) = 14.6, p<0.01), lymph node (chi(2) = 18.95, p<0.001) and distant metastasis (chi(2) = 11.3, p<0.001). In these cases, CEA mRNA, but not CEA, was entered in stepwise discriminant analysis to classify the presence of lymph node metastasis. CONCLUSIONS: The molecular detection of micrometastasis in the blood by means of CEA mRNA identification is feasible for colorectal, but not for gastric or pancreatic cancer staging. Further studies are needed in order to define the clinical utility of this marker also in follow-up protocols.

Adult↗
PubMed1999

Glucose metabolic alterations in isolated and perfused rat hepatocytes induced by pancreatic cancer conditioned medium: a low molecular weight factor possibly involved.

A serious insulin resistance characterizes pancreatic cancer-associated diabetes mellitus. Elsewhere, we demonstrated that MIA PaCa2 cultured cells secrete a soluble factor responsible for reduced glucose tolerance induced in SCID mice. The intracellular mechanism of insulin resistance was investigated in isolated and perfused rat hepatocytes incubated with MIA PaCa2 conditioned medium. Lactate production was reduced compared to hepatocytes incubated with control medium while 1,2-DAG was increased and PKC was activated in the hepatocytes incubated with MIA PaCa2 conditioned medium. This behavior was not reproduced treating the hepatocytes with the growth factors EGF, interleukin Ibeta, interleukin-6, and TGF-beta1. In an attempt to make a biochemical identification of the hypothesized tumor associated-diabetogenic factors we observed a low molecular weight protein in the conditioned medium, absent in the nonconditioned one, that may be responsible for the described behaviors.

Animals↗
PubMed1999

Serum antibodies anti-H. pylori and anti-CagA: a comparison between four different assays.

The authors compare efficacy of two ELISA assays (one supplied by DIAMEDIX [Delta Biological s.r.l.], and the other by RADIM [RADIM I]) in detecting total anti-H. pylori antibodies, and of two further ELISA methods (one supplied by EUROSPITAL [Helori CTX IgG] and the other by RADIM [RADIM 2]) in identifying anti-CagA antibodies, using sera from 69 controls (20 adults and 49 children) and from 96 patients, obtained before endoscopy. Seventy-three of the patients had H. pylori infection, while the remaining 23 were H. pylori negative (histology and polymerase chain reaction [PCR]). Fifty-two of the H. pylori positive patients, had cagA-positive strain infection, identified by PCR. The DIAMEDIX assay was found to be more sensitive (92%) than RADIM 1 (79%) in identifying H. pylori positive patients, irrespective of the infecting strain. On the other hand, the DIAMEDIX assay was less specific than RADIM 1 for H. pylori-negative patients (43% vs. 83%). However, when patients already treated for H. pylori infection were excluded from the group of H. pylori-negative patients, the DIAMEDIX assay had a specificity of 89%. In identifying anti-CagA antibodies, the kit supplied by RADIM (RADIM 2) had a sensitivity of 90% and a specificity of 94%, whereas that supplied by EUROSPITAL had a sensitivity of 100% and a specificity of 76%. The performances of the two methods in the identification of anti-CagA antibodies were found to be similar. The authors conclude that, in view of its high sensitivity, the DIAMEDIX assay may be useful in screening for H. pylori infection.

Adolescent↗
PubMed1999

Cytokines and the progression of liver damage in experimental bile duct ligation.

1. Cytokines are soluble factors whose action has been documented in physiological and pathological conditions. Some may be involved in the pathogenesis of cholestasis, whether of acute or chronic origin. 2. The aim of the present study was to evaluate the influence of epidermal growth factor (EGF), transforming growth factor (TGF)-beta 1, interleukin (IL)-6 and tumour necrosis factor (TNF) on cholestasis. Findings from Sprague-Dawley rats submitted to bile duct ligation for 1-28 days were compared with those from controls, which underwent laparotomy but not bile duct ligation. 3. Biochemical and morphological findings confirmed that the experimental procedure was successful. At the end of each follow-up period, the hepatic levels of the cytokines were determined and compared with liver histology findings. 4. The four cytokines studied showed different patterns of activation: hepatic levels of EGF, higher in the experimental than the control group, were comparable with the proliferative picture. The TGF-beta 1 pattern was correlated with data of periportal, perivenular and perineoductular fibrosis, confirming that this cytokine has a role in mediating the synthesis of matrix proteins. A fluctuating, phasic pattern was found for TNF in the experimental group, with high values on day 0, a decrease on the first and second postoperative days and then two peaks on days 8 and 14. Finally, immediately after surgical manipulation, high levels of IL-6 were found in the experimental group, followed by a decrease in levels until zero values were obtained. 5. This suggests that the obstructive condition produces several cytokine responses, each of which contributes to determine the cholestatic condition.

Animals↗
PubMed1999

Effect of cagA status on the sensitivity of enzyme immunoassay in diagnosing Helicobacter pylori-infected children.

BACKGROUND: The aims of our study were twofold. First, we sought to evaluate in symptomatic children the influence of the Helicobacter pylori genotype on gastritis, abdominal pain, and circulating anti-H. pylori IgG antibodies (anti-H. pylori IgG) or pepsinogen A (PGA) and C (PGC). Additionally, we sought to assess anti-H. pylori IgG, PGA, and PGC patterns in a large cohort (N = 921) of asymptomatic children. MATERIALS AND METHODS: In 183 symptomatic children, H. pylori infection and the presence of gastritis were evaluated by histology. In a subgroup of 20 H. pylori-positive children, the H. pylori genotype was evaluated also by polymerase chain reaction. Nine hundred and twenty-one asymptomatic children, aged 11 to 14 years, were studied by anti-H. pylori IgG, PGA, and PGC serum determination. RESULTS: The infection was found in 33 of 183 symptomatic children; among the 20 H. pylori-positive children for which the H. pylori genotype was available, cagA was present or absent in equal percentages. H. pylori infection was associated with more severe gastritis and higher serum levels of anti-H. pylori IgG and PGC but not with abdominal pain. In infected children, higher levels of anti-H. pylori IgG and the presence of abdominal pain were associated with infections caused by cagA-positive strains. In the cohort of 921 asymptomatic children, raised levels of anti-H. pylori IgG, PGA, and PGC were found in approximately 5% of the cases. CONCLUSIONS: Infection with cagA-positive H. pylori strains can be associated with increased frequency of reported abdominal pain and higher circulating levels of anti-H. pylori IgG. The serological assessment of H. pylori IgG using H. pylori antigens containing significant amounts of cagA protein may, therefore, underestimate the true prevalence of infection.

Abdominal Pain↗
PubMed1999

Cytokines modulate MIA PaCa 2 and CAPAN-1 adhesion to extracellular matrix proteins.

Variations in cancer cell adhesion to extracellular matrix (ECM) proteins might underlie an enhanced metastatic potential. ECM binding is mediated by cell-adhesion molecules, the membrane expression of which might be influenced by soluble mediators, such as cytokines. The aims of our study were to ascertain whether epidermal growth factor (EGF), transforming growth factor beta1 (TGF-beta1), interleukin 1alpha (IL-1alpha), or interleukin 1beta (IL-1beta) can modify MIA PaCa 2 (pancreatic cancer cell line) and CAPAN-1 (metastatic pancreatic cancer cell line) adhesion to fibronectin, laminin, or type I collagen, and whether these cytokines can shift the membrane expression of the hyaluronic acid receptor (CD44). EGF significantly enhanced MIA PaCa 2, but not CAPAN-1, adhesion to fibronectin, laminin, and type I collagen. TGF-beta1 reduced MIA PaCa 2 adhesion to type I collagen, but enhanced CAPAN-1 adhesion to fibronectin and laminin. IL-1alpha was found to enhance MIA PaCa 2 adhesion to fibronectin, while reducing adhesion to type I collagen, whereas IL-1beta reduced the adhesion to laminin. IL-1alpha enhanced CAPAN-1 adhesion to laminin in a dose-dependent manner; IL-1beta slightly increased the adhesion of these cells to laminin at low dosage, and to type I collagen at high dosage. Both IL-1alpha and IL-1beta reduced CD44 membrane expression of MIA PaCa 2, while TGF-beta1 increased the percentage of CD44-positive CAPAN-1 cells. We suggest that the effects on cell adhesion induced by different cytokines depend on the status of the target pancreatic cancer cell. EGF and, in part, IL-1alpha can favor nonmetastatic pancreatic cancer cell adhesion to ECM, possibly favoring tumor spread. Metastatic cells seem to lose the responsiveness to EGF, while becoming hyperresponsive to IL-1alpha. TGF-beta1 might exert an antidiffusive effect on primary, and a prodiffusive effect on metastatic pancreatic cancer cells. Only IL-1alpha, IL-1beta, and TGF-beta1 seem to influence CD44 membrane expression. All the results presented in this study were obtained in vitro, and in vivo studies are needed to verify whether the studied cytokines can favor or counteract pancreatic cancer spread.

Cell Adhesion↗
PubMed1999

Helicobacter pylori non-cytotoxic genotype enhances mucosal gastrin and mast cell tryptase.

AIMS: To determine the association, if any, between H pylori genotype and the gastric mucosal variations in the levels of gastrin, somatostatin, tryptase, and histamine. METHODS: 49 patients affected by duodenal ulcer and 48 by non-ulcer dyspepsia were studied. To identify the H pylori genotype, the presence of the cagA gene and vacA alleles m1, m2, s1, and s2 were analysed by polymerase chain reaction. Gastrin, somatostatin, tryptase, and histamine were measured in antral mucosal biopsies. RESULTS: 57 patients were infected with H pylori (30 with duodenal ulcer and 27 with non-ulcer dyspepsia). Gastrin and tryptase were increased in patients with H pylori infection, although the variations were statistically significant only for gastrin; somatostatin and histamine were not influenced by H pylori infection. In patients with non-ulcer dyspepsia the absence of the cagA gene and the presence of vacA alleles s2 and m2 were associated with higher values of tryptase and to a lesser extent of gastrin. These associations were not found in patients with duodenal ulcer. CONCLUSIONS: The cagA negative s2m2 strain of H pylori may be less dangerous for the gastric mucosa than other H pylori strains since it enhances tryptase production by gastric mucosal mast cells; this enzyme is thought to stimulate tissue turnover and favour wound healing.

Adolescent↗
PubMed1999

Polymorphonuclear oxidative burst after Helicobacter pylori water extract stimulation is not influenced by the cytotoxic genotype but indicates infection and gastritis grade.

H. pylori-associated gastric mucosal inflammation is characterized by the presence of polymorphonuclear (PMN) leukocyte infiltrate, which is more severe when the infecting strain is cagA positive. After appropriate stimuli, such as bacterial products, PMN release large amounts of oxygen derived free radicals and proteases, to kill the bacterium. H. pylori seems to be particularly resistant to the oxidative machinery of PMN, which can in turn damage the host gastric mucosa. We evaluated peripheral PMN oxidative burst response after stimulation with water extracts from cagA positive (WEcagA+) or negative (WEcagA-) H. pylori strains in infected (n=31) and non-infected patients (n=32) in comparison with healthy controls (n=16); the influence of gastric mucosal inflammatory infiltrate and activity grade on PMN oxidative burst were also assessed. PMN oxidative burst was measured by FACS analysis. H. pylori water extracts were obtained from bacterial culture. H. pylori genotype was determined by means of the polymerase chain reaction. The PMN oxidative burst in H. pylori infected patients was significantly higher than that in H. pylori negative or healthy controls, no differences being found when the results following WEcagA+ and WEcagA- stimulation were compared. The difference in PMN oxidative burst obtained after WEcagA- and E. coli (standard stimulus for PMN oxidative burst) stimulation discriminated H. pylori infected from non-infected patients with a sensitivity of 90% and a specificity of 97%. The grade of PMN oxidative burst correlated with PMN infiltration grade of the gastric mucosa. Our findings allow to conclude that PMN oxidative burst activation by H. pyloriWE is species- but not strain-correlated. PMN priming, probably consequent to the action of soluble mediators released by mononuclear cells, makes PMN hyper-responsive to H. pylori products, thus favoring the release in the gastric mucosa of infected patients of large amounts of oxygen-derived free radicals, which are not enough to eliminate the infection, but may contribute to damaging the gastric mucosa itself. Peripheral PMN oxidative burst response to H. pyloriWE might furthermore be of help in diagnosing H. pylori infection.

Adult↗
PubMed1999

[Biochemical markers of gastric functioning].

The serum determination of pepsinogen A (PGA) and pepsinogen C (PGC) might indicate gastric mucosal inflammation and atrophy. Body gastric mucosa produces both PGA and PGC, while antral mucosa produces only PGC. Therefore, diseases involving mainly the antrum, such as H. pylori infection, are mainly indicated by the variations in serum PGC than in serum PGA. In agreement, when the antral mucosa is infected by the more virulent cagA positive H. pylori strains, which cause severe inflammation, serum PGC significantly increases. Another indirect indicator of gastric inflammation is polymorphonuclear (PMN) oxidative burst after the stimulation with water extracts from H. pylori culture: this parameter is significantly increased in infected if compared to non-infected subjects. The higher oxidative burst response of peripheral PMN in infected patients, possibly consequent to the release of specific cytokines able to prime PMN towards H. pylori products, is unable to eliminate the infection, but it might concur in damaging the gastric mucosa.

Biomarkers↗
PubMed1998

Portal but not peripheral serum levels of interleukin 6 could interfere with glucose metabolism in patients with pancreatic cancer.

UNLABELLED: Interleukin 6 (IL-6), an autocrine growth factor for many tumors, seems to favour tumor spread to the liver. Our aims were first to evaluate the pattern of portal and systemic IL-6 levels in patients with pancreatic cancer (PC, n = 18) and chronic pancreatitis (CP, n = 22) compared with controls (CS, n = 20); and second, to ascertain whether there was any relation between IL-6 levels and tumor spread or PC-associated Diabetes mellitus. For all subjects, a fasting serum sample was obtained from a cubital vein; a portal serum sample was obtained from nine PC and three CP patients. In cubital and portal sera we measured IL-6, interleukin 1 beta (IL-1b), CA 19-9, c-reactive protein (CRP) and amylase. Systemic IL-6 levels were significantly higher in PC patients than in CS. In PC, portal IL-6 levels were significantly higher than the corresponding systemic values. The same pattern was found in the three CP patients, whereas IL-1b, CA 19-9, CRP and amylase portal levels were the same as systemic values. No correlation was found between PC stage and systemic or portal IL-6 levels. Portal IL-6 levels were correlated with the corresponding fasting serum glucose values. A significant correlation was found between IL-6 values and CRP, ALT, total bilirubin, GGT and creatinine, but not amylase. IN CONCLUSION: (1) Portal IL-6, which is partly of pancreatic origin, is first metabolised in the liver; (2) Systemic IL-6 reflects hepatic and renal functions rather than local conditions in the pancreas; (3) IL-6 does not appear to influence PC spread; (4) IL-6, which is released in large amounts by the inflamed pancreas, may contribute to determining diabetes, thus interfering with the signal transducing pathways involved in glucose metabolism in liver cells.

Aged↗
PubMed1998

Helicobacter pylori cytotoxic genotype is associated with peptic ulcer and influences serology.

OBJECTIVE: We studied 146 patients with peptic ulcer disease (n = 72), antral gastritis (n = 58), or duodenitis (n = 16) to ascertain whether the cytotoxic genotype of Helicobacter pylori (Hp) is associated with peptic ulcer disease and/or antral gastritis and whether it influences the circulating levels of total anti-Hp antibodies, anti-cagA antibodies, and pepsinogens. METHODS: A gastric juice sample was obtained from each patient. After DNA extraction, polymerase chain reaction was used to amplify the genes urease A (ureA), cagA, and vacA of Hp. RESULTS: A significant association was found between peptic ulcer disease and the cytotoxic genotypes, characterized by the presence of s1 and m1 alleles of vacA and by cagA. Patients with a cagA-positive genotype showed a significant increase in anti-cagA antibodies and also had significantly increased circulating levels of pepsinogen C. CONCLUSIONS: Cytotoxic Hp strains are mainly involved in determining peptic ulcer disease, but not antral gastritis. The higher levels of circulating pepsinogen C found in patients infected with cytotoxic genotypes may reflect the higher degree of inflammation sustained by these strains.

Adult↗
PubMed1998

Analysis of Helicobacter pylori vacA and cagA genotypes and serum antibody profile in benign and malignant gastroduodenal diseases.

BACKGROUND: Helicobacter pylori species comprise different strains, cytotoxic and non-cytotoxic, which can be identified on the basis of their genomic pattern. AIMS: (1) To evaluate the polymorphism of the vacA gene and to ascertain whether the cagA gene is present in patients with gastric adenocarcinoma. (2) To study the anti-H pylori antibody profile using western blotting. PATIENTS: Twenty one patients with gastric adenocarcinoma and 71 with H pylori associated benign disease (nine gastric ulcer, 29 duodenal ulcer, 25 antral gastritis, and eight duodenitis). METHODS: The polymerase chain reaction was used to verify the presence or absence of cagA and to study the polymorphism of vacA in gastric mucosal samples obtained during endoscopy for patients with benign diseases and at surgery for patients with gastric adenocarcinoma. Fasting sera were used to assess anti-H pylori antibodies against different H pylori antigens by western blotting. RESULTS: CagA gene and the allele s1 of vacA were significantly less frequent in patients with antral gastritis (60% and 60%) compared with patients with gastric adenocarcinoma (94% and 100%) and with other non-malignant gastroduodenal diseases (93% and 87%) (chi 2 = 16.01, p < 0.001; and chi 2 = 13.97, p < 0.01). In patients with gastric adenocarcinoma, antibodies against a 74 kDa H pylori antigen were less frequently found than in patients with benign diseases. CONCLUSIONS: H pylori infection caused by cagA positive/vacA s1 strains is a frequent finding in patients with gastric adenocarcinoma. Prospective studies are needed to confirm whether the low incidence of positive serological response to the 74 kDa H pylori antigen in patients with gastric adenocarcinoma is important.

Adenocarcinoma↗