Mario Correale

Serum levels of galectin-3 and its ligand 90k/mac-2bp in colorectal cancer patients

Galectin-3 is an endogenous lectin that binds glycan epitopes of cell membrane and some extracellular glycoproteins such as integrins and laminin. Galectin-3 is involved in several biological activities including regulation of cellular cycle, modulation of adhesion and tumor progression and metastasis. 90K/Mac-2BP glycoprotein is also a serum galectin-3 ligand. 90K is able to modulate the immune reaction against tumors and viruses and its level increases in sera of several neoplastic diseases. In our study, we have evaluated levels of both glycoproteins in sera of non metastatic colon cancer patients. Interestingly, galectin-3 ranged higher in cancer patients than in controls (p<0.0001), particularly in more differentiated tumors (p<0.04). Moreover, 90K mean values ranged higher in right-side than in left-side colon cancer. In conclusion, serum galectin3 might represent a useful biomarker to evaluate colon cancer transformation and, together with its ligand 90K, could contribute to the characterization of colon cancer.

Serum 90K/MAC-2BP Glycoprotein in Patients with Liver Cirrhosis and Hepatocellular Carcinoma: a Comparison with α-Fetoprotein

Abstract Glycoprotein 90K/MAC-2BP is a member of the scavenger receptor cystein-rich protein superfamily, which is thought to be involved in immune surveillance, defending the body against pathogens and cancer. 90K serum levels are elevated in patients with cancer of various origins and in viral infections, such as human immunodeficiency virus and hepatitis C virus (HCV). Because in patients with HCV-related cirrhosis the incidence of hepatocellular carcinoma (HCC) is high, in the present paper we examined, by means of an enzyme-linked immunosorbent assay, the 90K serum levels in 103 patients with liver cirrhosis, and in 69 with HCC, and compared them to α-fetoprotein, the reference tumor marker for this neoplasm. Serum levels of 90K (cut-off 14 μg/ml) were elevated both in cirrhosis (39%) and HCC (46%) compared to controls (14.1 μg/ml vs. 10.6 μg/ml in cirrhosis, and 14.8 μg/ml vs. 9.1 μg/ml in HCC, p≤0.001). There was a significant association with the presence of anti-HCV antibodies. 90K was found to be a non-specific tumor marker which is complementary to α-fetoprotein on the basis of its probable different biological significance. In fact, 74% of HCC patients had at least one positive marker. Combined use of 90K and α-fetoprotein could improve the sensitivity of a single test in the diagnosis of HCC.

Effects of low concentrations of Regorafenib and Sorafenib on human HCC cell AFP, migration, invasion, and growth in vitro†‡

Sorafenib was shown in clinical trial to enhance survival in hepatocellular carcinoma (HCC) patients, but with minimal tumor shrinkage. To correlate several indices of HCC growth at various drug concentrations, HCC cells were grown in various low concentrations of two multikinase inhibitors, Regorafenib (Stivarga) and Sorafenib (Nexavar) and their effects were examined on alpha‐fetoprotein (AFP), cell growth, migration, and invasion. In two AFP positive human HCC cell lines, AFP was inhibited at 0.1–1 µM drug concentrations. Cell migration and invasion were also inhibited at similar low drug concentrations. However, 10‐fold higher drug concentrations were required to inhibit cell growth in both AFP positive and negative cells. To investigate this concentration discrepancy of effects, cells were then grown for prolonged times and sub‐cultured in low drug concentrations and then their growth was re‐tested. The growth in these drug‐exposed cells was found to be slower than cells without prior drug exposure and they were also more sensitive to subsequent drug challenge. Evidence was also found for changes in cell signaling pathways in these slow‐growth cells. Low multikinase inhibitor concentrations thus modulate several aspects of HCC cell biology. J. Cell. Physiol. 228: 1344–1350, 2013.

Serum Lipid Profile in Colorectal Cancer Patients with and without Synchronous Distant Metastases

Objective: In this study, the serum lipid profile, including total cholesterol (TC), triglycerides (TG), high-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C), has been investigated in colorectal cancer patients (CRC) with and without synchronous distant metastases. The aim of this study was to verify whether the presence of metastases was associated to serum lipid abnormalities, and whether lipoprotein abnormalities were linked to the nutritional status. Methods: The fasting serum lipid profile was examined in 84 CRC patients using colorimetric methods. To determine the nutritional status, the body mass index (BMI) was calculated and serum albumin was measured. Results: Patients with distant metastases showed significantly higher levels of TC, LDL-C and the LDL-C/HDL-C ratio than patients without metastases (p< 0.05). The presence of metastases was positively associated with TC, LDL-C and the LDL-C/HDL-C ratio, being independent of sex, age and BMI. Conclusions: Elevated serum lipid levels may facilitate the development of distant metastasis in CRC patients.

Mutagenic activity of some platinum complexes with monodentate and bidentate amines

Abstract The effect of bridging with an ethylene chain the two aminic nitrogens cis -coordinated to the metal in a platinum-dichloro-diamine complex has been examined by studying forward mutagenesis in strains of Salmonella typhimurium carrying hisG46 and hisD3052 mutations and differing at the uvrB locus. While the complexes with the monodentate amines NH 3 and α-methylbenzylamine (mba) exhibit strong mutagenic activity, the corresponding species with chelating diamines, 1,2-diaminoethane (en) and N,N ′-bis(α-methylbenzyl)1,2-diaminoethane (mben), show much weaker activity. Moreover, the latter complexes appear to be more active via ‘frame shift’ than ‘base substitution’ mechanisms and do not differentiate appreciably between cells differing in the rfa locus. Complexes with amines bearing alkyl substituents of opposite chirality ( R -mba and S -mba, R,R -mben and S,S -mben) were tested separately and appeared to have comparable activity.

Mutagenic activity of some platinum complexes: Chemical properties and biological activity†

In order to find correlations between chemical reactivity and biological activity, we have started an investigation on the mutagenic activity of different platinum‐chloroamine complexes towards different strains of Salmonella Typhimurium. The first class of compounds examined includes complexes of general formula cis‐[PtCl2(amine)(L)] in which L represents a strong trans‐labilizing ligand. Using dimethylsulphoxide as solvent these compounds were not toxic or mutagenic, on the contrary in acetone they were toxic towards all strains of bacteria independently from their excision‐repair ability. An entirely different behaviour was exhibited by a second class of compounds having general formula cis‐[PtCl2(amine)2] which includes also cis‐dichlorodi‐ammoniaplatinum(II) (cis‐DDP). These compounds were much less toxic than the previous ones in acetone and were mutagenic; moreover they were able to discriminate between different bacteria strains. Therefore some complexes were active only towards hisG46/pKM101 stra...

Ultrasound Evaluation and Correlates of Fatty Liver Disease: A Population Study in a Mediterranean Area

BACKGROUND The aim of this study was to evaluate the distribution of fatty liver-nonalcoholic (NAFL) and alcoholic (AFL)-and its association with metabolic syndrome and its components in a population sample from a Mediterranean area. METHODS A sample of 2974 subjects (1679 males, 1295 females, age range 30-89 years) was randomly drawn from the population of a town in southern Italy. The survey visit included a validated semiquantitative food frequency questionnaire, anthropometric measurements, a blood sample taken in the morning after overnight fasting, as well as abdominal ultrasound examination to evaluate liver fat with a standardized scoring system. The 2001 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definition of the metabolic syndrome was adopted. RESULTS In this Mediterranean population, where alcohol intake is mostly as wine with meals, NAFL is present in 36.8% of men and 25.7% of women and AFL in 13.8% of men and 5.5% of women. NAFL and AFL are associated with metabolic syndrome and its characteristics, body mass index (BMI), and visceral and subcutaneous fat (in AFL subjects, only in women) measured by ultrasound. Stratifying by BMI and controlling for confounders (age, height, smoking habit, and alcohol consumption), in overweight and obese subjects, liver and visceral fat are associated with the metabolic syndrome both in men and women and subcutaneous fat only in women. In normal weight subjects, only liver fat in men is associated with the metabolic syndrome. CONCLUSIONS Fatty liver is highly prevalent in this Mediterranean population and is associated with metabolic syndrome in overweight and obese men and women as well as in men with normal BMI.

Are 90K/MAC-2BP serum levels correlated with poor prognosis in HCC patients? Preliminary results

In this study we assessed the prognostic significance of 90K/MAC-2BP serum levels in a group of 40 hepatocellular carcinoma patients. This glycoprotein is a new, interesting serum marker that reflects the immune reaction of the host against certain viral infections and tumors such as breast, ovarian and pancreatic cancer. Hepatocellular carcinoma (HCC) is one of the most widespread tumors in the world. AFP is currently the most useful marker for HCC, in spite of its poor diagnostic sensitivity. In this study 40 cirrhotic HCC patients were enrolled. The prevalence of viral hepatic infections in this group was 73% for HCV, 8% for HBV, and 8% for both viruses. Thirteen percent of the patients showed non-virus-related liver damage. 90K serum levels were assayed by an ELISA kit and AFP levels by a chemiluminescent enzyme immunometric system. The overall survival curves were estimated by the Kaplan-Meier method, taking into account age, sex, 90K and AFP serum levels. Statistical analysis showed a highly significant influence on overall survival of age below 70 years and 90K serum levels below the cutoff of 14 ng/mL. Serum AFP (< or = 20 ng/mL) had positive prognostic value only when it was associated with 90K levels (p < 0.02, log-rank).

Effect of a Low Glycemic Index Mediterranean Diet on non-alcoholic fatty liver disease. A randomized controlled clinici trial

IntroductionNon-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common form of liver disease worldwide affecting all ages and ethnic groups and it has become a consistent threat even in young people. Our aim was to estimate the effect of a Low Glycemic Index Mediterranean Diet (LGIMD) on the NAFLD score as measured by a Liver Ultrasonography (LUS).DesignNUTRIzione in EPAtologia (NUTRIEPA) is a population-based Double-Blind RCT. Data were collected in 2011 and analyzed in 2013-14.Setting/participants98 men and women coming from Putignano (Puglia, Southern Italy) were drawn from a previous randomly sampled population-based study and identified as having moderate or severe NAFLD.InterventionThe intervention strategy was the assignment of a LGIMD or a control diet.Outcome measuresThe main outcome measure was NAFLD score, defined by LUS.ResultsAfter randomization, 50 subjects were assigned to a LGIMD and 48 to a control diet. The study lasted six months and all participants were subject to monthly controls/checks. Adherence to the LGIMD as measured by Mediterranean Adequacy Index (MAI) showed a median of 10.1. A negative interaction between time and LGIMD on the NAFLD score (-4.14, 95% CI -6.78,-1.49) was observed, and became more evident at the sixth month (-4.43, 95%CI -7.15, -1.71). A positive effect of the interaction among LGIMD, time and age (Third month: 0.07, 95% CI 0.02, 0.12; Sixth month: 0.08, 95% CI 0.03,0.13) was also observed.ConclusionsLGIMD was found to decrease the NAFLD score in a relatively short time. Encouraging those subjects who do not seek medical attention but still have NAFLD to follow a LGIMD and other life-style interventions, may reduce the degree of severity of the disease. Dietary intervention of this kind, could also form the cornerstone of primary prevention of Type 2 Diabetes Mellitus (T2DM) and cardiovascular disease.

Serum 90K/Mac-2 Binding Protein (Mac-2BP) as a Response Predictor to Peginterferon and Ribavirin Combined Treatment in Hcv Chronic Patients

90K/Mac-2BP glycoprotein is involved in the immune defense against a variety of neoplasms and viral infections, modulating the activity of several effectors such as natural killer cells. Quite interestingly, 90K/Mac-2BP is associated to a poor response to interferon (IFN) α in hepatitis C virus (HCV) infected patients. Here, in 70 consecutive HCV chronic patients, we have evaluated 90K basal levels as a response predictor to combined therapy with Peginterferon and Ribavirin. We have found higher 90K levels in genotype 1/4 than in genotype 2/3 (p = 0.006) and in 62.5% of non-responders than in 20% of responders (p < 0.001). Genotype 1/4, higher 90K and gamma glutamyl transferase (γGT) levels resulted independently associated to a status of refractoriness to therapy. Consequently, evaluation of 90K serum levels seems to be a promising useful marker of response to combined therapy in HCV disease.