Epidemiological, clinical and pathological characteristics of gastric neoplasms in the province of Cremona: the experience of the first population-based specialized gastric cancer registry in Italy.

BACKGROUND: The gastric cancer incidence rate differs widely across geographical areas. In Italy, in the province of Cremona the incidence is high, compared to the national situation. For this reason a specialized population-based registry was set up. METHODS: The collection encompasses all gastric cancers diagnosed in the three districts of the province since January 1, 2010. The main data sources were the pathological and Hospital Discharge Records and patient clinical charts. Only diagnoses of primary gastric cancer were considered. For each case the following variables were registered: personal data, medical history and symptoms at diagnosis; imaging assessments performed, details on surgery and other treatments received; genetic background and biomolecular characteristics; social and environmental factors. RESULTS: As of November 2017, 1087 cases were collected; of which 876, diagnosed up to December 2015, were analyzed. Male/female ratio was 1.4. The European Age-standardized Incidence Rate was 41.4 for males and 28.3 for females as compared to a national average of 33.3 and 17.0 respectively. Median age at diagnosis was 73 for male and 78 for female. Helicobacter Pylori infection was present in fewer than 20% of cases. HER-2 gene was amplified in about 25% of cases. Primary tumour location was the gastro-esophageal junction or cardia in 17.5% in males and 8.3% in females. The majority of cases (58.3%) were diagnosed at an advanced stage and overall only 41.2% underwent surgery. Median overall survival was 14.8 months for men and 18.5 for women. Age standardized 5-year relative survival was 31.4% for men and 40.5% for females. Neoadjuvant treatment was performed in fewer than 10% of patients who underwent surgery, and the rate of postoperative therapy adherence was low. DISCUSSION: This study shows a high gastric cancer incidence in the province of Cremona, with a geographical spread across different districts. Moreover, a high percentage of gastric cancers were detected at an advanced stage of disease and a low rate of 5-year relative survival was registered. Based on these findings, effective preventive interventional health strategies and screening procedures need to be implemented to reduce the impact of this pathology in this geographical area.

Influenza virosomes are an efficient delivery system for respiratory syncytial virus-F antigen inducing humoral and cell-mediated immunity.

In the present study we investigated the efficacy of a new potential vaccine constituted of the respiratory syncytial virus (RSV)-F protein associated with influenza virosomes (RSV-F/IRIV) in combination with the mucosal adjuvant Escheriagen (Escherichia coli heat-labile toxin), administered intranasally (i.n.) to BALB/c mice. After an intramuscular "priming" with influenza virus vaccine, group A of mice was i.n. immunized with of RSV-F/IRIV+heat-labile toxin (HLT), groups B and C were inoculated i.n. with F-RSV+HLT and IRIV+HLT, respectively. The results showed that the virosomal delivery system greatly potentiate immune responses in animals. All mice immunized with the RSV-F/IRIV+HLT developed a mucosal IgA response and a high level of serum IgG. A balanced Th1/Th2 cytokine profile was observed in mice immunized with RSV-F/IRIV+HLT, while a Th2 response was observed in mice immunized with RSV-F+HLT. Histological analysis of lung tissue of RSV challenged mice did not reveal a vaccine-enhanced pulmonary eosinophilia. These results show that i.n. immunization of BALB/c mice with RSV-F/IRIV in combination with HLT can be considered a promising approach for the development of an efficacious human vaccine.

Macrophage migration inhibitory factor in prostatic adenocarcinoma: correlation with tumor grading and combination endocrine treatment-related changes.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a ubiquitary cytokine whose expression has been investigated in tumors, showing a correlation between tumor aggressiveness and production of this protein by neoplastic cells. The aim of our study was to correlate MIF expression with tumor grade (Gleason scoring system) and histopathological changes after combined endocrine treatment (CET) of prostate adenocarcinoma. METHODS: We analyzed MIF immunoreactivity in 124 paired needle biopsies and radical prostatectomy specimens from 62 prostate cancer patients, of which 20 had been treated with CET. RESULTS: In untreated prostates, MIF expression significantly correlated with tumor grading, being stronger in low-grade than in high-grade adenocarcinoma. In treated prostates, histopathological changes also correlated with MIF immunoreactivity, but not in a significant manner. CONCLUSIONS: The results of the current study demonstrated that with histological dedifferentiation, prostate adenocarcinoma cells show a reduced MIF expression. This finding may be the consequence of a reduced MIF synthesis or the result of an enhanced and altered secretion by tumor cells into the surrounding stroma. The consequent abnormal interaction between MIF and environmental factors might influence tumor growth and diffusion. On the other hand, the minor but not significantly reduced MIF expression by tumor cells after CET seems to exclude a hormonal regulation of MIF secretion.

Modulation of Na+/K+ pump in intact erythrocytes by cardioglycosides, steroid hormones and ouabain-like compounds.

1. Pure erythrocytes preparations, free from platelets and white cells, were incubated for a long time without hemolysis. 2. Dose-response experiments performed with (a) cardioglycosides (ouabain and K-strophantoside), (b) steroid hormones and their glucuronides (tetrahydrocortisol, oestradiol and the respective 3-glucuronic derivatives) and (c) ouabain-like compounds purified in our laboratory (0.7 kDa and 2-4 kDa respectively) emphasise a modulatory effect [activation of Na+ efflux rate and K+ uptake at very low ligand concentrations, inhibition at higher levels; maximum enhancement of cation transport: (a) and (b) 10-0.1 nM (+40-50%), (c) 1-0.01 nM (2.5-fold)]. 3. Binding experiments show upward-curved Scatchard graphs, with the Kd values of 50 nM and 18 microM and the Bmax values of 10.2 and 984.5 fmol/100 microliters RBC (red blood cells) respectively.

Modulatory effect of two cardioglycosides on reconstituted Na+/K(+)-ATPase in proteoliposomes.

1. Na,K-ATPase was extracted from Cavia cobaya kidneys, solubilized with nonionic detergent C12E8 (octaethyleneglycol dodecyl monoether) in mixed lipid-detergent-protein micelles. The Na,K-ATPase specific activity was 30-35 IU/mg protein. 2. The enzyme was reconstituted in vesicles, made of phosphatidylethanolamine and cholesterol: an enhancement of +60% in specific activity was obtained. 3. Two different vesicle-types were carried out: open liposomes (partially organized membranes) and closed liposomes. 4. Proteoliposomes were employed for measuring the modulatory effect of two cardioglycosides: ouabain and digoxin. 5. Inhibition of the Na,K-ATPase activity revealed apparent Ki of 1.25 microM for ouabain and 0.25 microM for digoxin in open liposomes, and apparent Ki of 0.75 microM for ouabain and of 1.75 microM for digoxin in closed liposomes. 6. Maximum enhancement of enzymatic activity was found at concentrations of 5-0.5 nM for ouabain and 5-1 nM for digoxin in open liposomes, and 25-1 nM for both digoxin and ouabain in closed liposomes.

Extraction, purification and characterization of ADH1 from the budding yeast Kluyveromyces marxianus.

The enzyme ADH1 has been extracted and purified from the budding yeast Kluyveromyces marxianus, and its enzymatic activity has been compared, with the ADH1 extracted and purified in the same way from the well known yeast Saccharomyces cerevisiae. K. marxianus ADH1 has an optimal temperature higher than the S. cerevisiae enzyme (45-50 degrees vs 35 degrees C), a better stability to pH variations in the oxidative reaction (pH optimum 7.5), a lower Michaelis constant for acetaldehyde, and a good catalytic activity both for fermentative and oxidative reactions. In fact, while in Saccharomyces the constants ratio (velocity constant fermentation/velocity constant oxidation) is about 20,000, in Kluyveromyces the same ratio is only 15. Even if these two Genera are quite related (they belong to the same subfamily) it seems that their ADH1s possess different catalytic properties.