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D Basso

Publications and source records attributed to D Basso.

At least 19 recordsLinked to original sources

A locally adaptive statistical procedure (LAP) to identify differentially expressed chromosomal regions.

MOTIVATION: The systematic integration of expression profiles and other types of gene information, such as chromosomal localization, ontological annotations and sequence characteristics, still represents a challenge in the gene expression arena. In particular, the analysis of transcriptional data in context of the physical location of genes in a genome appears promising in detecting chromosomal regions with transcriptional imbalances often characterizing cancer. RESULTS: A computational tool named locally adaptive statistical procedure (LAP), which incorporates transcriptional data and structural information for the identification of differentially expressed chromosomal regions, is described. LAP accounts for variations in the distance between genes and in gene density by smoothing standard statistics on gene position before testing the significance of their differential levels of gene expression. The procedure smooths parameters and computes p-values locally to account for the complex structure of the genome and to more precisely estimate the differential expression of chromosomal regions. The application of LAP to three independent sets of raw expression data allowed identifying differentially expressed regions that are directly involved in known chromosomal aberrations characteristic of tumors. AVAILABILITY: Functions in R for implementing the LAP method are available at http://www.dpci.unipd.it/Bioeng/Publications/LAP.htm

Algorithms↗

Insights in the laboratory diagnosis of celiac disease.

The present report focuses on the diagnosis of celiac disease and its pathogenesis, which depends on a genetic predisposition (HLA DQ2 or DQ8 haplotypes), gluten ingestion and T cell activation, type II transglutaminase (TG2), the autoantigen recognized by the antiendomysial antibody playing a key role. IgA class antibody anti-environmental (gliadin) and endogenous (TG2) antigens are present in the sera of patients with celiac disease. The anti-TG2 antibody has the best available diagnostic accuracy, especially when measured employing second generation ELISA tests, which use the human TG2 antigen, or immunochemiluminescent assay, which is highly sensitive. A diagnosis of celiac disease must always be confirmed by the histological evaluation of multiple duodenal mucosa specimens, and serology is recommended for follow-up controls.

Antibodies↗

Killer genes in pancreatic cancer therapy.

This review describes: 1. The main genetic alterations found in pancreatic cancer (EGF-R overexpression, SST-2 somatostatin receptor loss of expression, k-ras, p53 mutations and DPC4 mutations) and the effect of their replacements by gene therapy on tumor growth; 2. The use of suicide genes (HSV-TK and CD) for pancreatic cancer gene therapy in vitro and in vivo; 3. The implications for pancreatic cancer treatment when using cytotoxic bacterial toxins; 4. Viral and non-viral delivery systems for the transfer of therapeutical genes into pancreatic cancer cells. Overall both the correction of pancreatic cancer cells main genetic alterations and the use of suicide genes allow only partial tumor regression in vitro and in vivo. The lack of a 100% effect for any studied strategy considered alone, indicates the need for combined therapies to achieve a satisfactory treatment of this tumor.

Animals↗

Plasma chromogranin A in patients with prostate cancer improves the diagnostic efficacy of free/total prostate-specific antigen determination.

INTRODUCTION: We ascertained whether plasma chromogranin A enhances the power of serology assessing prostate cancer (PC). MATERIALS AND METHODS: We studied 56 PC and 83 benign prostatic hyperplasia (BPH) patients. In the sera we measured total prostate-specific antigen (tPSA) and free PSA (fPSA) and calculated the ratio between fPSA and tPSA (f/tPSA). In plasma samples the levels of chromogranin A (CgA) were also assayed. RESULTS: PC patients had higher CgA (p < 0.005) and tPSA (p < 0.05) levels, and a lower f/tPSA ratio (p < 0.001), than BPH patients. When f/tPSA and CgA were combined, the diagnostic sensitivity was enhanced (57-73%), while the specificity had only an 8% reduction (from 89 to 80%). CgA was only correlated to the Gleason PC score (p < 0.05). CONCLUSIONS: CgA determination in PC may enhance the diagnostic accuracy of the f/tPSA assay and provides useful information on the tumor grade.

Aged↗

Color Doppler velocimetry and three-dimensional color power angiography of cervical carcinoma.

OBJECTIVES: To investigate the blood flow within invasive cervical carcinoma by transvaginal two-dimensional (2D) color spectral Doppler and three-dimensional (3D) color power angiography and to correlate these parameters with the clinicopathological characteristics. METHODS: Seventy-four patients with invasive cervical carcinoma were enrolled for the analysis. Squamous cell carcinoma serum antigen levels (SCC) were obtained for all the patients. Sections of all malignant tissues were analyzed for tumor expression of cyclooxygenase-2 (COX-2). All patients underwent color and spectral Doppler examination and 44 patients had 3D color power angiography. Color spectral Doppler parameters (color score, lowest resistance index (RI), highest peak systolic velocity (PSV)) and 3D color power angiography indices (relative color, average color, flow measure) of FIGO I/II cervical cancers were compared with those obtained in a control group of 24 patients with a normal uterine cervix. Pulsed Doppler parameters and the 3D vascular indices were compared with clinicopathological parameters, SCC serum antigen levels and tumor COX-2 expression. RESULTS: At color Doppler analysis 72 patients (97%) showed intralesional detectable vessels. Color spectral Doppler and 3D-derived parameters were significantly different in FIGO I/II cervical cancers compared with those in women with a normal cervix. A significantly higher color score (P = 0.0008), lower RI (P = 0.032) and higher PSV (P = 0.004) were associated with a tumor diameter > or =4 cm compared with smaller tumors. The highest PSV was significantly higher in patients with FIGO stage III/IV compared with FIGO stage I/II (P = 0.0069). There was a direct correlation between PSV and SCC (r = +0.44, P = 0.003). The median relative color was significantly higher in patients with a higher color score (P = 0.0006). No statistically significant correlations were found between 3D color power angiography parameters and the clinicopathological characteristics or between the 3D vascular parameters and biological factors. CONCLUSIONS: Alterations of 3D ultrasound-derived vascular indices were found in patients with cervical cancer compared with those with a normal cervix. Moreover, some vascular indices proved to be associated with tumor size. The assessment of a possible clinical role of 2D and 3D ultrasound-derived vascular indices in cervical cancer deserves further investigation.

Adult↗

Allergy to wine.

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Adult↗

Altered glucose metabolism and proteolysis in pancreatic cancer cell conditioned myoblasts: searching for a gene expression pattern with a microarray analysis of 5000 skeletal muscle genes.

BACKGROUND AND AIMS: We verified whether conditioned media (CM) from pancreatic cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3) alter glucose metabolism and gene expression profiles (microarray experiment with a platform of 5000 skeletal muscle cDNA) in mice myoblasts. METHODS: Myoblasts were incubated with control or pancreatic cancer CM for 24 and 48 hours. RESULTS: Lactate significantly increased in CM compared with non-conditioned myoblasts. No variations in expression levels of the main genes involved in glycolysis were found in CM myoblasts. Propionyl coenzyme A carboxylase and isocitrate dehydrogenase 3 beta genes, which encode enzymes of the tricarboxylic acid cycle, were overexpressed, while IGFIIR and VAMP5 genes were underexpressed in CM myoblasts. PAFAH1B1 and BCL-2 genes (intracellular signal transduction) and the serine protease cathepsin G (proteolysis), were overexpressed in CM myoblasts. Tyrosine accumulation in CM myoblasts suggested that proteolysis overcomes protein synthesis. Sorcin, actin alpha, troponin T1, and filamin A were underexpressed in CM myoblasts. CONCLUSIONS: Our findings demonstrate that pancreatic cancer cell conditioned media enhanced lactate production and induced proteolysis, possibly by altering expression levels of a large number of genes, not only those involved in protein biosynthesis and degradation or glucose metabolism, but also those involved in the tricarboxylic acid cycle and in vesicle traffic.

Aged↗

Suicide gene therapy with HSV-TK in pancreatic cancer has no effect in vivo in a mouse model.

AIM: To study in vivo whether pancreatic cancer tumour growth and metastasis can be modified by a gene construct with HSV-TK suicide gene and IL2 co-expression. METHODS: Seventy-eight female SCID mice were i.p. inoculated with retrovirally transduced or control MIA PaCa 2, CAPAN-1 and PANC-1 cell lines. The animals were then randomly selected for saline or ganciclovir (GCV) treatment from the second week, for a total of two weeks. RESULTS: Most inoculated mice developed tumour nodules and spleen metastases. The liver was colonized by control CAPAN-1 and MIA PaCa 2, but not by PANC-1. Tumours in transduced MIA PaCa 2 cell injected mice were smaller, and in transduced CAPAN-1 injected mice larger, than in control-inoculated mice. There were increased pancreatic and decreased spleen metastases from transduced CAPAN-1, and diminished liver involvement from transduced MIA PaCa 2. No differences were found between mice inoculated with transduced and control PANC-1 cell lines. GCV treatment had no effect on tumour's size or metastases. CONCLUSIONS: The HSV-TK suicide gene does not confer GCV sensitivity to pancreatic cancer in this in vivo model. Different pancreatic cancer cell lines cause different growth and metastasis patterns after inoculation in SCID mice, possibly because of variations in their inherent characteristics. The different effects of our vector on cell growth and metastasis may be attributable to the effects of the immunostimulatory cytokine IL2.

Animals↗

Helicobacter pylori babA2, cagA, and s1 vacA genes work synergistically in causing intestinal metaplasia.

AIMS: To determine any associations between the Helicobacter pylori genes babA2, oipA, cagA and the s and m alleles of vacA. In addition, to verify whether these genes work synergistically or independently in causing gastritis, peptic ulcer, and intestinal metaplasia. METHODS: One hundred and sixty seven H pylori positive patients were studied (52 antral gastritis, 41 diffuse gastritis, 41 peptic ulcer, and 33 duodenitis). Helicobacter pylori virulence genes were amplified by means of the polymerase chain reaction. RESULTS: Significant associations were found between babA2 and the other H pylori genes studied. When considered singly, all the genes were associated with disease diagnosis, inflammation, and intestinal metaplasia. Four H pylori groups were defined. Group A: cagA-, s2m2, babA2-; group B: cagA+, s1m1, babA2+; group C: cagA+, s1m2, babA2+; group D: cagA+, s1m2, babA2-. Group A infecting strains were associated with less severe endoscopic and inflammatory conditions, whereas group B strains were associated with the worst endoscopic and inflammatory findings. Intestinal metaplasia was a rare finding in group A infected patients (< 10%), whereas it was frequent in those infected with group B strains (48%). CONCLUSIONS: The H pylori genes cagA, oipA "on", s1 and m1 vacA, and babA2 are associated with each other, possibly as a result of shared selective pressure. When coexpressed by the same H pylori strain, cagA, s1 and m1 vacA, and babA2 work synergistically in worsening inflammation. Infections caused by strains coexpressing cagA, s1m1 vacA, and babA2 are those at higher risk for intestinal metaplasia.

Adhesins, Bacterial↗

Helicobacter pylori virulence genes and host IL-1RN and IL-1beta genes interplay in favouring the development of peptic ulcer and intestinal metaplasia.

Helicobacter pylori infection outcome might depend on genotypic polymorphisms of both the bacterium and the host. We ascertained: (1) the functionality of H. pylori oipA gene; (2) the polymorphism of the hostinterleukin (IL-1beta) gene (-31 C/T) and of the IL-1RN gene (intron 2 VNTR); (3) the association between the above genes and the histological and pathological outcome of H. pylori infection. One hundred and sixty-five H. pylori positive and 137 H. pylori negative subjects (23 gastric adenocarcinoma, 58 peptic ulcer, 221 gastritis) were studied. oipA was sequenced, IL-1beta was RFLP analysed. Antral and body mucosal biopsies were histologically evaluated. Functional oipA genes were correlated with cagA gene; both genes were significantly associated with gastritis activity, peptic ulcer and gastric adenocarcinoma. In these patients heterozygousIL-1RN 1/2 and IL-1beta C/T genotypes were more frequent than in gastritis patients. Intestinal metaplasia was associated with cagA, functional oipA and IL-1RN 2 allele. In conclusion, peptic ulcer and the preneoplastic intestinal metaplasia are associated with H. pylori virulence genes and with IL-1RN 2 host allele. An interplay between bacterial virulence factors and cytokines genotypes, is probably the main route causing H. pylori infection to lead to benign mild disease, benign severe disease or preneoplastic lesions.

Adenocarcinoma↗

Prevalence of coeliac disease in primary biliary cirrhosis and of antimitochondrial antibodies in adult coeliac disease patients in Italy.

BACKGROUND: Although an association between primary biliary cirrhosis and coeliac disease has recently been reported in Northern Europe, there are still conflicting data concerning this issue. AIM: To evaluate both the prevalence of coeliac disease in a series of primary biliary cirrhosis patients and that of antimitochondrial antibodies in a series of adult biopsy proven coeliac disease patients from Northern Italy. PATIENTS AND METHODS: A total of 87 primary biliary cirrhosis patients (79 female, 8 male) were screened for both IgA-transglutaminase antibodies and antiendomysium antibodies and, in those with either IgA-transglutaminase antibodies or antiendomysium antibodies positivity, upper endoscopy with distal duodenum biopsy was offered. In those who refused upper endoscopy, the intestinal permeability test with lactulose/mannitol excretion was performed. RESULTS: Antiendomysium antibodies positivity was detected in 3 subjects (3.4%), all of whom had serum IgA-transglutaminase antibodies above the normal range, and fulfilled the diagnosis of coeliac disease. Of 21 other patients with serum IgA-transglutaminase antibodies above the normal range, 17 underwent upper endoscopy which revealed normal duodenum architecture. The remaining 4 patients underwent the lactulose/mannitol excretion test which was within the normal range. Sera from 108 adult coeliac disease patients were tested for antimitochondrial antibodies and positivity was found in 4 patients (3.7%): all had normal liver biochemistry tests, whereas 2 of them also presented thyroid disease. Antibodies directed to the 74-kDa polypeptide of antimitochondrial antibodies were found in 3 out of 4 antimitochondrial antibodies+ve patients. CONCLUSIONS: These results suggest an association between primary biliary cirrhosis and coeliac disease similar to that observed in the Northern European series. In conclusion, screening for coeliac disease with antiendomysium antibodies in primary biliary cirrhosis is justified, and screening for antimitochondrial antibodies is advisable in adult coeliac disease patients.

Aged↗

Role of anti-transglutaminase (anti-tTG), anti-gliadin, and anti-endomysium serum antibodies in diagnosing celiac disease: a comparison of four different commercial kits for anti-tTG determination.

The aims of this study were: (1) to compare the diagnostic efficacy for celiac disease (CD) diagnosis of serum determination of anti-gliadin (AG) (IgA and IgG) and anti-endomysium (AE) with that of anti-transglutaminase (AtTG); and (2) to compare the accuracy of four different assays to measure AtTG. We studied 72 children: the histological diagnosis of CD was made in 38 cases and excluded in the remaining 34 children. In fasting sera we measured AE, AG-IgA and IgG, and AtTG, the latter with four different commercial kits (Eurospital, Medipan, Inova, Arnika). Moreover AtTG was measured in a group of 58 CD children after a gluten-free diet. AE was positive in all but 1 case of CD patients (sensitivity = 97%); false positive results were found in 1/34 controls (specificity = 97%). When a specificity of 95% was fixed, the sensitivities were 97% for AE, 83% for AG-IgA, and 63% for AG-IgG; the sensitivities of anti-tTG were 90, 84, 84, and 75% when measured with Eurospital, Medipan, Inova, and Arnika kits respectively. The new AtTG seems to be accurate enough to be proposed as a noninvasive diagnostic tool for CD diagnosis; the 4 kits analyzed showed similar diagnostic efficacy.

Adolescent↗

Serum protein profiles of patients with pancreatic cancer and chronic pancreatitis: searching for a diagnostic protein pattern.

In this study, 13 sera from patients with pancreatic cancer, 9 from chronic pancreatitis and 10 from healthy subjects were analyzed by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The MALDI mass spectra revealed the presence of several low molecular weight peptides, among which some were detected only in the sera from both pathological conditions. On the other hand many peptides were observed only in control sera, and were absent in the sera from the two diseases. Therefore, MALDI analysis of the low molecular weight fraction (<10 000 Da) of sera from patients with pancreatic diseases enabled us to identify the presence of some disease-related signals and also some signals characteristic of normal subjects.

Aged↗

Colorectal cancer metastatic phenotype stimulates production by fibroblasts of N-terminal peptide of type III collagen: clinical implications for prognosis.

In this study we assessed whether the serum levels of the N-terminal peptide of type III collagen (PIIIP), an index of type III collagen synthesis, are influenced by colorectal cancer stage, and whether "in vitro" fibroblast growth and PIIIP production could be altered by tumor tissues obtained from metastatic and nonmetastatic colorectal cancer. 208 colorectal cancer patients (115 colon and 93 rectum) were studied; 54 were stage I, 62 stage II, 37 stage III and 55 stage IV. PIIIP serum levels were significantly higher in stage IV as compared to all other patient groups. The 5-year survival of stage I, stage II, stage III and stage IV patients were 87%, 88%, 32% and 20%, respectively. In the subgroup of stage I and stage II patients considered together, PIIIP (> 0.5 U/ml), but not CEA (> 5 microg/l) serum levels, were predictive for survival. Fibroblast growth was significantly inhibited, while PIIIP production was significantly enhanced, when these cells were conditioned with colorectal cancer homogenates obtained from patients with distant metastases, than from those without distant metastases. In conclusion, colorectal tumors, when metastatic, stimulate fibroblasts' PIIIP synthesis and the serum levels of this peptide might predict patients' outcome after radical surgery.

Carcinoembryonic Antigen↗

Different effects of H. pylori water extracts on cytokines, pepsinogen C and gastrin mucosal release in patients with or without duodenal ulcer.

In the present study we ascertained whether cagA positive and negative H. pylori strains release water soluble products that can influence the production of gastric mucosal cytokines and endocrine (gastrin) or exocrine (pepsinogen C) secretion in 23 H. pylori positive and 19 H. pylori negative patients. Antral biopsies were obtained to classify inflammation, activity, atrophy, intestinal metaplasia and H. pylori density grade. The cagA gene was identified by means of the polymerase chain reaction (PCR) in H. pylori positive colonies after culture of mucosal samples. Three antral biopsies from each patient were incubated with (1.) Water extracts from cagA positive, (2.) Water extracts from cagA negative strains or (3.) H2O (control) at 37 degrees C in a CO2 incubator for 24 hrs. Gastrin, pepsinogen C, IL-1 beta, IL-8, GMCSF, and TNF alpha were measured in the supernatants and mucosal homogenates. H. pylori infection was significantly associated with an increased antral inflammation and activity (chi 2 = 21.7, p < 0.001 and chi 2 = 42.0, p < 0.001), and increased mucosal levels of IL-1 beta, IL-8 and TNF alpha. Water extracts from cagA positive strains enhanced the release of PGC in mucosal biopsy supernatants (p < 0.05) when patients were considered overall and the release of TNF alpha (p < 0.05) when only patients with duodenal ulcer were considered. Water extracts from cagA negative strains stimulated gastrin secretion (p < 0.05). None of the remaining cytokines were influenced by H. pylori water extracts. In conclusion, pepsinogen C and TNF alpha can be induced by cagA positive water extracts and may contribute to damage the gastric and duodenal mucosa. Our findings indicate that in patients with H. pylori infection the increase of the mucosal levels of IL-1 beta and IL-8 does not depend on H. pylori water soluble products, but probably depends on the entire bacterium.

Adult↗

[Diagnosis of Helicobacter pylori infection: comparison of techniques].

UNLABELLED: Several diagnostic assays are available for evaluating Helicobacter pylori infection: histological examination, culture of gastric biopsies, urea breath test and serology. Recently a new enzyme immunoassay has been introduced for the detection of H. pylori antigens in stool samples (HpSA). The aim of our study was to evaluate and compare diagnostic efficacy of HpSA with histological examination, culture, urea breath test and serology in a group of 95 patients. Patients were classified H. pylori positive (43) or negative (52) on the basis of histology, culture and urea breath test. HpSA optical densities were significantly higher in infected patients compared to those obtained in H. pylori-negative patients (t = 5.47, p < 0.001). Overall, with a fixed cut-off of 0.1 unit of optical density, the sensitivity was 79% and the specificity 100%. In the H. pylori positive patients, HpSA optical density correlated with bacterial load histologically evaluated in the gastric antrum (r = 0.405, p < 0.05) and was inverse correlated with levels of serum IgG elicited against H. pylori (r = -0.315, p < 0.05). Considering patients with a positive HpSA finding and/or levels of anti-H. pylori antibodies upper than 30 U/mL, sensitivity in detecting infected patients was 98%. IN CONCLUSION: (1) immunodetection of H. pylori antigens in stools is a good alternative of breath test; (2) a reduction in H. pylori density grade might be accompanied by low HpSA optical density, leading to a false negative result and (3) combining the HpSA determination with the serum detection of anti-H. pylori antibodies a better clinical sensitivity is obtained.

Adult↗

Antigastric autoantibodies in Helicobacter pylori infection: role in gastric mucosal inflammation.

UNLABELLED: The aim of the study was to ascertain whether there is an association between the presence of serum parietal cell autoantibodies (PCA) and: (1) Helicobacter pylori infection; (2) the presence and degree of gastritis and intestinal metaplasia; and (3) the H. pylori infecting strain. Gastric mucosal biopsies were obtained from 49 consecutive patients in order to assess and grade gastritis, make a histological diagnosis, and culture and genotype H. pylori. H. pylori infection was present in 26 patients (group 1), had been present in 17 patients (group 2), and the remaining 6 (group 3) had never had the infection. The infecting strain was cagA positive in 21 of 26 group 1 patients. Positive PCA results were found in 84%, 76%, and 14% of patients in groups 1, 2, and 3, respectively. PCA results were correlated with anti-H. pylori antibody titers (P<0.05). In group 2 patients, PCA were associated with the degree of antral gastritis (Fisher's exact test P<0.05). cagA status was not associated with the presence of PCA (chi2=0.68, NS). The frequency of positive findings for PCA in group 2 was higher in patients with (90%) than in those without (50%) intestinal metaplasia. IN CONCLUSION: (1) H. pylori infection is associated with the production of PCA, which, after eradication of the infection, persist and might contribute to the persistent antral chronic gastritis and intestinal metaplasia; (2) the gastric lesions associated with infections sustained by the more-virulent H. pylori strains do not appear to be due to the induction of antigastric autoantibodies.

Adolescent↗