Roles of p53, NF-κB and the androgen receptor in controlling NGAL expression in prostate cancer cell lines

2018

Neutrophil gelatinase-associated lipocalin (NGAL a.k.a lipocalin 2, lnc2) is a secreted protein which can form a complex with matrix metalloproteinase-9 (MMP9). This MMP9/NGAL complex has been associated with metastasis. MMP9 and NGAL are detected in the urine of patients afflicted with many different types of cancer, including prostate cancer. The effects of p53, NF-κB and the androgen receptor (AR) on the expression of NGAL was examined in four prostate cancer cell lines. Prostate cancer cell lines that are AR negative and expressed either mutant or no p53 (DU145 and PC3) displayed higher levels of NGAL expression compared to the prostate cancer cell lines (LNCaP and 22Rv-1) which are AR …

Histamine and spontaneously released mast cell granules affect the cell growth of human hepatocellular carcinoma cells

2007

The role of mast cells in tumor growth is still controversial. In this study we analyzed the effects of both histamine and pre-formed mediators spontaneously released by mast cells on the growth of two human hepatocellular carcinoma cell lines, HA22T/VGH and HuH-6, with different characteristics of differentiation, biological behavior and genetic defects. We showed that total mast cell releasate, exocytosed granules (granule remnants) and histamine reduced cell viability and proliferation in HuH-6 cells. In contrast, in HA22T/VGH cells granule remnants and histamine induced a weak but significant increase in cell growth. We showed that both cell lines expressed histamine receptors H(1) and …

Advances in Targeting Signal Transduction Pathways

2012

// James A. McCubrey 1 , Linda S. Steelman 1 , William H. Chappell 1 , Lin Sun 1,2 , Nicole M. Davis 1 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Lucio Cocco 3 , Camilla Evangelisti 4 , Francesca Chiarini 4 , Alberto M. Martelli 3,4 , Massimo Libra 5 , Saverio Candido 5 , Giovanni Ligresti 5 , Grazia Malaponte 5 , Maria C. Mazzarino 5 , Paolo Fagone 5 , Marco Donia 5 , Ferdinando Nicoletti 5 , Jerry Polesel 6 , Renato Talamini 6 , Jorg Basecke 7 , Sanja Mijatovic 8 , Danijela Maksimovic-Ivanic 8 , Michele Milella 9 , Agostino Tafuri 10 , Joanna Dulinska-Litewka 11 , Piotr Laidler 11 , Antonio B. D’Assoro 12 , Lyudmyla Drobot 13 , Kazuo Umezawa 14 , Giuseppe Montalto 15 , Melchiorre Cer…

Guinea pig transglutaminase immunolinked assay does not predict coeliac disease in patients with chronic liver disease

2001

BACKGROUND—It has been suggested that serological screening for coeliac disease (CD) should be performed in patients with chronic unexplained hypertransaminasaemia.
AIMS—To evaluate the specificity for CD diagnosis of serum IgA antitissue transglutaminase (tTG) determination in consecutive patients with chronic hypertransaminasaemia using the most widely utilised ELISA based on tTG from guinea pig as the antigen.
PATIENTS AND METHODS—We studied 98 patients with chronic hypertransaminasaemia, evaluated for the first time in a hepatology clinic. Serum anti-tTG and antiendomysial (EmA) assays were performed. Patients positive for EmA and/or anti-tTG were proposed for intestinal biopsy. Finally…

Steatocrit test: Normal range and physiological variations in infants

1990

In order to define the normal values of steatocrit during the first 3 months of life and the normal correlation between fecal fat content and steatocrit values, 60 full-term healthy unweaned infants (30 bottle-fed, 15 breast-fed, and 15 mixed-fed) were studied. The steatocrit micromethod was performed in these babies at 7, 14, 21, 28, 45, and 90 days after birth. Steatorrhea often occurs during the first month and then decreases, as shown by the fall in the steatocrit curve from 7th to 28th day in our subjects; at 45 days, few babies have steatorrhea. The 90th percentile profile of steatocrit values shows a value of 25% at the first week of life and a value of 13% at the fourth week. After …

Regulation of GSK-3 activity by curcumin, berberine and resveratrol: Potential effects on multiple diseases.

2017

Natural products or nutraceuticals promote anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway. This review will focus on the effects of curcumin (CUR), berberine (BBR) and resveratrol (RES), on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway, with a special focus on GSK-3. These natural products may regulate the pathway by multiple mechanisms including: reactive oxygen species (ROS), cytokine receptors, mirco-RNAs (miRs) and many others. CUR is present the root of turmeric (Curcuma longa). CUR is used in the treatment of many disorders, especially in those involving inflammatory p…

Persistent cow's milk protein intolerance in infants: the changing faces of the same disease

1998

Background Recent research has shown that cow's milk protein intolerance (CMPI) often persists beyond 4 years of age. Aims To evaluate the clinical and immunological characteristics of a group of infants with persistent CMPI. Patients and methods Twelve infants (6 m, 6f) with persistent CMPI were followed up from birth until a median age of 5 years. The patients underwent CMP challenge each year to evaluate CMP-tolerance. As controls we followed 26 infants (12 m, 14 f) with CMPI that resolved within 1–2 years. Results A family history of atopic disease was found in 10/12 patients with persistent CMPI and in 10/26 controls (P < 0.01). Clinical presentation changed over time: at onset symptom…

Molecular mechanisms of sorafenib action in liver cancer cells.

2012

Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced hepatocellular carcinoma (HCC). However, as the clinical application of sorafenib evolves, there is increasing interest in defining the mechanisms underlying its anti-tumor activity. Considering that this specific inhibitor could target unexpected molecules depending on the biologic context, a precise understanding of its mechanism of action could be critical to maximize its treatment efficacy, while minimizing adverse effects. Two human HCC cell lines (HepG2 and Huh7), carrying different biological and genetic characteristics, were used in this study to examine the intracellular events leading …

Non invasive tools for the diagnosis of liver cirrhosis

2014

Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibros…

Prevalence of diabetes mellitus and impaired glucose tolerance in cystic fibrosis.

1990

The aim of this study was to evaluate the prevalence of impaired glucose tolerance or diabetes mellitus in 99 patients (53 M, 46 F; mean age 10.5 +/- 6.9 years), with cystic fibrosis. Glucose tolerance was evaluated in all patients without overt diabetes using the oral glucose tolerance test (OGTT). Six patients showed a pathological OGTT and 2 patients had insulin-requiring diabetes mellitus. The mean age of the patients with impaired glucose tolerance was significantly higher than that of the subjects with normal glucose metabolism (p less than 0.0001). Patients with overt diabetes mellitus were the oldest subjects in the study group.

Diagnostic use of fructosamine assay in the control of type II diabetes mellitus.

1988

In an attempt to evaluate the usefulness of fructosamine assay in monitoring type II diabetes, 142 diabetic patients were investigated. Fructosamine values were found to be higher in patients on insulin treatment than on oral hypoglycemic agents. In order to evaluate the metabolic control by using the correlated variations of F, Gm and HbAlc, the patients were subdivided into many control classes: mean values of fructosamine were higher in poorly controlled patients. Fructosamine however correlated better with glycemia in patients with recent variations in metabolic state than HbAlc. It was concluded that fructosamine is a good index for short-term metabolic control, and if used in an integ…

Alteration of the YY1/RKIP ratio is a frequent event in hepatocellular carcinoma

2009

Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.

2012

The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Certain components of these pathways, RAS, NF1, BRAF, MEK1, DUSP5, PP2A, PIK3CA, PIK3R1, PIK3R4, PIK3R5, IRS4, AKT, NFKB1, MTOR, PTEN, TSC1, and TSC2 may also be activated/inactivated by mutations or epigenetic silencing. Upstream mutations in one signaling pathway or even in downstream components of the same pathway can alter the sensitivity of the cells to certain small molecule inhibitors. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of components of these cas…

HEPATIC EXPRESSION OF CYCLOOXYGENASE-2 IN NON-ALCOHOLIC FATTY LIVER DISEASE

2008

Siero-prevalenza di marcatori di infezione da virus dell’epatite B, C ed HIV in una coorte di immigrati africani a Palermo, Sicilia.

2011

Obiettivi In Italia il 7% della popolazione è rappresentata da immigrati, dei quali oltre 127.000 sono legalmente residenti in Sicilia. Di questi, il 30,3% proviene da Paesi africani, prevalentemente dell’area sub-Sahariana, dove l’epidemiologia delle infezioni virali da virus dell’epatite B (HBV), dell’epatite C (HCV) e dell’immunodeficienza acquisita (HIV) è molto differente da quella europea. Il presente studio è stato condotto per valutare la sieroprevalenza di marcatori di infezione da HBV, HCV ed HIV in una coorte di individui immigrati dall’Africa sub-Sahariana e residenti in Sicilia. Metodi Un’analisi retrospettiva è stata condotta su un panel di 176 sieri, consecutivamente prelevat…

Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis…

2019

Wong, Grace LH/0000-0002-2863-9389; Wong, Vincent WS/0000-0003-2215-9410; Mangia, A/0000-0002-2600-3555; Brahmania, Mayur/0000-0002-4671-1479; Chan, Henry Lik-Yuen/0000-0002-7790-1611; Brouwer, Willem Pieter/0000-0001-8713-1481; Feld, Jordan/0000-0003-2640-2211; Tanwandee, Tawesak/0000-0001-7634-0843; Jaroszewicz, Jerzy/0000-0003-0139-4753; Chuaypen, Natthaya/0000-0002-5415-510X

GLP-1 receptor agonists and reduction of cardiometabolic risk: Potential underlying mechanisms

2018

Type 2 diabetes mellitus (T2DM) is a metabolic condition with an elevated impact on cardiovascular (CV) risk. The innovative therapeutic approaches for T2DM - incretin-based therapies (IBTs), including glucagon-like peptide 1 (GLP-1) receptor agonists, have become popular and more widely used in recent years. The available scientific data from clinical studies and clinical practice highlights their beyond glucose-lowering effects, which is achieved without any increase in hypoglycaemia. The former effects include reduction in body weight, lipids, blood pressure, inflammatory markers, oxidative stress, endothelial dysfunction, and subclinical atherosclerosis, thus reducing and potentially pr…

Soluble complement receptor type 1 (sCR1) in chronic liver diseases: serum levels at different stages of liver diseases.

1998

SUMMARYComplement receptor type 1 (CR1) is an integral membrane protein of many haematopoietic cells and plays an important role in the clearance of complement-associated immune complexes, favouring their transport to liver and spleen macrophages. A small amount of soluble CR1 (sCR1) is also found in plasma and might originate directly from release of leucocytes and other circulating cells. In previous studies, an increase in serum sCR1 level has been observed in liver cirrhosis and end-stage renal failure. High levels have also been found in patients with some haematologic malignancies. sCR1 serum levels were measured using a specific double sandwich ELISA assay. The present study demonstr…

Abnormal liver function in brucellosis

2008

We assessed the prevalence of impaired liver function in 47 patients suffering from brucellosis consecutively admitted to our department over the last five years. Parameters of liver function and ultrasound of the upper abdomen were performed at entry and at the end of treatment. On admission, mean transaminase values were elevated and significantly higher than at recovery (p 0.001): 38 percent and 53 percent of patients had elevated baseline values of GOT and GPT vs 13 and 19% at the end of treatment, respectively. Mean serum values of alkaline phosphatase (AP) were within normal limits on admission, although in 12 of them serum values were elevated. The same proportion was seen for gamma-…

Leucocyte Interferon-alpha for Patients with Chronic Hepatitis C Intolerant to Other alpha-Interferons

2003

Background: Alpha-interferon (α-IFN) is the treatment of choice for chronic hepatitis C but most patients experience adverse effects which sometimes lead to the suspension of therapy. Recently, higher doses of α-IFN or prolonged therapy have increased the number of cases of intolerance. Study Design: In this open study we evaluated the efficacy and safety of leucocyte interferon-alpha (IFNα) [6MU three times a week] in 43 patients with chronic hepatitis C who had been intolerant to previous treatment courses with recombinant or lymphoblastoid IFNα. All patients were treated for 6 months and followed-up for an additional 6 months. End of treatment responders were patients in whom hepatitis C…

Effectiveness of Enteric-Coated Preparations on Nutritional Parameters in Cystic Fibrosis

1988

To evaluate the effectiveness of enteric-coated pancreatic enzyme supplements in comparison to conventional preparations of ingested enzyme on growth and nutritional parameters of patients with cystic fibrosis, we conducted a long-term study involving 40 patients. The data reproduced here were recorded after 6 months of therapy with powder-containing capsules or with enteric-coated products. Fat absorption was estimated by measurement of steatorrhoea with the steatocrit method. All parameters studied improved after enteric-coated pancreatic enzyme therapy, with a statistically significant increase in weight, cholesterol and haemoglobin values. Furthermore, the number of patients with positi…

Combined Dyslipidemia: Should the Focus be LDL Cholesterol or Atherogenic Dyslipidemia?

2012

As the population becomes more obese and the prevalence of diabetes and the metabolic syndrome increases, low-density lipoprotein-cholesterol (LDL-C) may lose its value as a sole predictor for cardiovascular risk among lipids. Combined dyslipidemia is typically characterized by elevations in LDL-C and triglyceride levels, often accompanied by decreased high-density lipoproteincholesterol (HDL-C) concentrations and increased levels of small, dense LDL. This common disorder results from overproduction of hepatically synthesized apolipoprotein B in very low-density lipoproteins. In the last few years most of the international scientific guidelines as well as several expert panels have confirme…

Emerging Raf inhibitors

2009

The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway is often activated by genetic alterations in upstream signaling molecules. An integral component of this pathway, BRAF, is also activated by mutation, especially in melanoma and thyroid cancers. The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway has profound effects on proliferative, apoptotic and differentiation pathways as well as the sensitivity and resistance to chemotherapeutic drugs.This review discusses targeting of Raf which could control abnormal proliferation in cancer and other proliferative diseases. The important roles that genetics plays in the response of patients to Raf inhibitors is also evalua…

Può la misura della densità tumorale essere considerata un parametro attendibile nella valutazione della risposta ai trattamenti antiangiogenetici ed…

2012

Relazione tra linfoadenopatia del legamento epatoduodenale e risposta alla terapia anti-virale in pazienti con epatite cronica HCV-correlata

2002

IgA antiendomysial antibodies on the umbilical cord in diagnosing celiac disease. Sensitivity, specificity, and comparative evaluation with the tradi…

1996

The possibility of assaying antiendomysial antibodies (EmA) on the human umbilical cord instead of monkey esophagus has recently been suggested. We therefore evaluated in patients with celiac disease (CD) the sensitivity and specificity of EmA and of antigliadin antibodies (AGA) for both umbilical cord and monkey esophagus.We studied 36 patients with CD and atrophy of the intestinal mucosa (median age, 1.4 years), 14 patients with CD on gluten-free diet for 8-12 months (median age, 3.0 years), 36 controls without gastrointestinal disease (median age, 4.0 years), and 72 patients with cow's milk protein enteropathy (CMPE) (median age, 1.2 years). AGA and EmA on monkey esophagus were assayed w…

Effects of berberine, curcumin, resveratrol alone and in combination with chemotherapeutic drugs and signal transduction inhibitors on cancer cells-P…

2017

Over the past fifty years, society has become aware of the importance of a healthy diet in terms of human fitness and longevity. More recently, the concept of the beneficial effects of certain components of our diet and other compounds, that are consumed often by different cultures in various parts of the world, has become apparent. These “healthy” components of our diet are often referred to as nutraceuticals and they can prevent/suppress: aging, bacterial, fungal and viral infections, diabetes, inflammation, metabolic disorders and cardiovascular diseases and have other health-enhancing effects. Moreover, they are now often being investigated because of their anti-cancer properties/po…

Hepatocellular carcinoma: comparison of two different periods at the same center.

2010

Aims: To analyze the main etiological factors and some clinical characteristics of patients with HCC at diagnosis and to compare them with those we described ten years ago. Methods: 179 patients were included in Group 1, while 132 patients were included in Group 2. For all patients age, sex, serum markers of hepatitis B and C viruses, alcohol consumption, serum alpha feto-protein (AFP) levels and the main liver function parameters at HCC diagnosis were recorded. Results: Mean age was 66.0 years for Group 1 and 69.0 for Group 2 (P=0.005). HCV was responsible for 80.3% of HCC cases in Group 2 versus 72% in Group 1 (P=0.005). HBV alone and co-infection of HCV+HBV decreased, but not significant…

Effects of ectopic expression of NGAL on doxorubicin sensitivity.

2012

Neutrophil gelatinase-associated lipocalin (NGAL, a.k.a Lnc2) is a member of the lipocalin family which has diverse roles including stabilizing matrix metalloproteinase-9 from auto-degradation and as siderocalins which are important in the transport of iron. NGAL also has important biological functions involved in immunity and inflammation as well as responses to kidney damage. NGAL expression has also been associated with certain neoplasia and is important in the metastasis of breast cancer. Many advanced cancer patients have elevated levels of NGAL in their urine and it has been proposed that NGAL may be a prognostic indicator for certain cancers (e.g. breast, brain, and others). NGAL exp…

Viral clearance in HCV viraemic patients with normal aminotransferase after combination therapy: a controlled, open-labelled study

2004

Extreme thrombocytosis as a sign of coeliac disease in the elderly: case report

2002

Increase in the number of blood platelets to over 1 000 000/mm 3 in elderly patients is generally considered secondary to a myeloproliferative or neoplastic disease. To report the case of an elderly woman hospitalized for extreme thrombocytosis associated with severe anaemia, who was found to be suffering from coeliac disease. The patient, aged 83 years, was hospitalized presenting with fatigue. Laboratory tests showed microcytic hypochromic anaemia (haemoglobin 4 g/dl) and extreme thrombocytosis (platelet count 1 400 000/mm 3 ). Physical examination was normal, with the exception of marked thinness. There was no evidence of macroscopic bleeding from the gastrointestinal or genitourinary tr…

Expression of IAPs and alternative splice variants in hepatocellular carcinoma tissues and cells.

2005

IAPs (inhibitors of apoptosis proteins) might have a major role in the apoptotic resistance that marks many cancers. The studies on IAPs in human HCC have focused on survivin or XIAP, indicating that their new or increased expression in this tumor is associated with a more unfavorable prognosis. The present results corroborate these findings, emphasizing the role that the coordinated expression of different IAPs and alternative splice variants might play in the adverse biology of hepatocellular carcinoma.

Genetic Determined Downregulation of Both Type 1 and Type 2 Cytokine Pathways Might Be Protective against Pancreatic Cancer

2009

Many cytokine polymorphisms have been studied for associations with susceptibility to breast, gastric, liver, lung, prostate, and ovarian cancer without conclusive results. The cytokine network, indeed, is characterized by complex interactions, and the final biological effect of a single genetic variation depends on the balance among different molecular signals. As is well known, Th1/Th2 cytokine unbalanced production might predispose to different pathologies, cancer included. In general, a prolonged type 1 inflammatory response might allow that cells accumulating enough "genetic hits" are promoted to neoplastic transformation. On the other hand, IL-13-producing cells through the IL-13/IL-4…

Retreatment of interferon plus ribavirin unresponsive patients with chronic hepatitis C with peginterferon alfa 2a plus mycofenolatemofetile or pegin…

2005

Comorbidities impact and de-prescribing in elderly with HCV-related liver disease: analysis of a prospective cohort.

2021

AbstractManagement for HCV has undergone a notable change using direct-acting antiviral drugs (DAAs), which are safe and effective even in elderly. Here, we define impact of comorbidities, concomitant medication and drug–drug interactions in elder patients with HCV related disease before starting DAAs regimen. We analyzed data of 814 patients prospectively enrolled at our Unit within the web based model HCV Sicily Network. Out of 814, 590 were treated with DAAs and 414 of them were older than 65 years. We divided those 414 in two groups, one including 215 patients, aged between 65 and 74 years, and another with 199 patients, aged of 75 years and over. Charlson Comorbidity Index (CCI) was as…

The Changing Epidemiology of Hepatocellular Carcinoma :  Experience of a Single Center

2019

Aims. To analyze the main etiological factors and some clinical features of patients with hepatocellular carcinoma (HCC) at diagnosis and to compare them with those we described ten years ago. Materials and Methods. We compared two groups of patients with HCC, Group 1 consisting of 132 patients (82 M, 50 F) diagnosed in the 2003–2008 period and Group 2 including 119 patients (82 M, 37 F) diagnosed in the 2013–2018 period. For all patients, age, sex, viral markers, alcohol consumption, serum alpha-fetoprotein (AFP) levels, and the main liver function parameters were recorded. The diagnosis of HCC was based on AASLD, EASL guidelines. The staging was classified according to the “Barcelona Clin…

Insufficienza renale acuta in paziente con HCC recentemente sottoposto a chemioembolizzazione transarteriosa

2008

Epidemiology, Risk Factors, and Natural History of Hepatocellular Carcinoma

2002

The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio. The heterogeneous geographic distribution reflects the epidemiologic impact of the main etiologic factors and environmental risk, which are the hepatitis B (HBV) and hepatitis C (HCV) viruses. The percentage of cases of hepatocellular carcinoma attributable to HBV worldwide is 52.3% and is higher in Asia where the serop…

Long-term follow-up of hepatitis B e antigen-negative patients treated with peginterferon α-2a: progressive decrease in hepatitis B surface antigen i…

2012

Viral clearance in HCV viraemic patients with normal alanine aminotransferase after combination therapy: a controlled, open-labelled study

2004

Summary Background : In patients with chronic hepatitis C virus infection and persistently normal alanine aminotransferase levels, liver fibrosis has been reported in 0–22% of cases and advanced liver disease in 5–10% of cases. Aim : To determine whether patients with persistently normal alanine aminotransferase levels clear infection after anti-viral therapy at equal or different rates from infected patients with raised alanine aminotransferase levels. Methods : Thirty-five hepatitis C virus RNA-positive patients with fibrosis at liver histology (Group 1) were matched for genotype, sex, age and histology with patients with raised alanine aminotransferase levels (Group 2). Both groups were …

Prevalence of overweight and obesity in a rural southern Italy population and relationships with total and cardiovascular mortality: the Ventimiglia …

2001

OBJECTIVE: We investigated the prevalence of overweight and obesity and their relationships with the main cardiovascular risk factors in the population of Ventimiglia di Sicilia, a rural village in Southern Italy characterized by low cholesterol levels and by a low incidence of early coronary heart disease mortality. We related all deaths to body weight and fat distribution during an 8 y follow-up. DESIGN: Cross-sectional and prospective observational study. SUBJECTS: A total of 835 free-living individuals, 363 males and 472 females, of age between 20 and 69 y. MEASUREMENTS: In all participants body weight, waist-to-hip ratio (WHR), cardiovascular risk factors and plasma lipids were measure…

Epidemiology, risk factors, and natural history of hepatocellular carcinoma

2002

The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio. The heterogeneous geographic distribution reflects the epidemiologic impact of the main etiologic factors and environmental risk, which are the hepatitis B (HBV) and hepatitis C (HCV) viruses. The percentage of cases of hepatocellular carcinoma attributable to HBV worldwide is 52.3% and is higher in Asia where the serop…

Gene expression profiling of human liver cancer cells following celecoxib tretment

2010

Comparison of BT-PABA test and fecal chymotrypsin measurements in normal subjects and diabetic patients

1990

A N-benzoil-L-tyrosil-PABA test on 6h urine collection, a plasma PABA assay 2 h after administration and a fecal chymotrypsin assay were performed on 66 patients (36 controls and 30 type 2 diabetic patients on insulin therapy). All patients were hospitalized and without gastrointestinal and renal disease. The mean values of plasmatic PABA and fecal chymotrypsin were significantly lower in the diabetic group than in the controls (p less than 0.025 and p less than 0.01, respectively), although they remained within normal range. But this was not the case for PABA urinary excretion values. This may indicate a slower but more protracted PABA absorption during the third or fourth hour with the re…

Cyclooxygenases in hepatocellular carcinoma

2006

Many epidemiological studies demonstrate that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) reduce the incidence and mortality of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase (COX) enzymes are well-known targets of NSAIDs. However, conventional NSAIDs non-selectively inhibit both the constitutive form COX-1, and the inducible form COX-2. Recent evidence indicates that COX-2 is an important molecular target for anticancer therapies. Its expression is undetectable in most normal tissues, and is highly induced by pro-inflammatory cytokines, mitogens, tumor promoters and growth factors. It is now well-established that COX-2 is chronically overexpr…

What changed in the Italian internal medicine and geriatric wards during the lockdown

2021

A total of 48 internal medicine or geriatric wards among the 93 adhering to the register REPOSI answered an online questionnaire aimed to investigate the characteristics and activities of converted and non-converted wards in the crucial period of the first wave of the epidemic, 22 February-4 May 2020

Prevalence and genomic variability of transfusion transmitted virus in Italian cryptogenic chronic liver disease and healthy blood donors

2002

Abstract Background. Infection with transfusion transmitted virus, a new member of the Parvoviridae family, has been found in patients both with chronic and fulminant post-transfusion cryptogenic hepatitis. Aim. To evaluate the prevalence and clinical impact of transfusion transmitted virus infection in Italy. Patients and Methods. Studies were carried out on 256 patients and control subjects from three centres from Northern, Central and Southern Italy (92 nonA-nonC chronic hepatitis, 10 acute non fulminant cryptogenic hepatitis, 41 hepatitis C virus-related chronic hepatitis and 113 blood donors). Serum transfusion transmitted virus was detected by nested polymerase chain reaction using tw…

Compliance with the clinical practice guidelines for the management of hepatitis B and C virus-related chronic liver disease: a survey based on hospi…

2013

Benefit of weight bosed dosoges of Ribavirin (RBV) in combinotion with Peg-lnterferon (PeglFN) a2a in naive patients with HCV2 and HCV3: results of a…

2012

Expression of WISPs and of their novel alternative variants in human hepatocellular carcinoma cells

2005

WISPs (Wnt-induced secreted proteins) are members of the CCN (CTGF/Cyr61/Nov) family involved in fibrotic disorders and tumorigenesis. They have a typical structure composed of four conserved cysteine-rich modular domains, but variants of CCN members lacking one or more modules, generated by alternative splicing or gene mutations, have been described in various pathological conditions. WISP genes were first described as downstream targets of the Wnt signaling pathway, which is frequently altered in human hepatocellular carcinoma (HCC). In the present study, WISP mRNA expression was analyzed by RT-PCR in four human HCC cell lines (HepG2, HuH-6, HuH-7, HA22T/VGH). Our results show for the fir…

503 ALLELIC VARIANTS OF CYP2E1 GENE IN HEPATOCARCINOMA PATIENTS AND IN HEPATIC TUMOR CELL LINES

2011

Aromatase and amphiregulin are correspondingly expressed in human liver cancer cells

2009

Human hepatocellular carcinoma (HCC) is associated with high mortality rates, being the third most common cause of cancer death worldwide. Although estrogens have been implicated in HCC, their potential role in development and/or progression of this malignancy remains unclear. In this study we investigated mRNA and protein expression of aromatase (Aro) and amphiregulin (AREG) in relation to estrogen receptors (ERs), in HepG2, Huh7, and HA22T human malignant liver cell lines, using RT-PCR and Western blot analyses. Aro expression was significantly higher (approximately 13-fold, P= 0.003) in HepG2 cells than in Huh7 cells, while no Aro expression could be detected in HA22T cells. Interestingl…

GSK-3 in liver diseases: Friend or foe?

2020

Liver diseases, including hepatitis due to hepatitis B or C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma pose major challenges for overall health due to limited curative treatment options. Thus, there is an urgent need to develop new therapeutic strategies for the treatment of these diseases. A better understanding of the signaling pathways involved in the pathogenesis of liver diseases can help to improve the efficacy of emerging therapies, mainly based on pharmacological approaches, which influence one or more specific molecules involved in key signal transduction pathways. These emerging therapies are very promising for the prevention and treatment of …

Hepatic and circulating levels of PCSK9 in morbidly obese patients: Relation with severity of liver steatosis

2020

Non-alcoholic fatty liver disease (NAFLD) is becoming the main cause of liver disease in Western countries, especially in morbidly obese patients (MOPs). The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recently studied because of its possible involvement in the pathogenesis of NAFLD, but its role, at least in MOPs, is still controversial. The aim of this study was to clarify the correlation between the circulating levels of the PCSK9 protein (cPCSK9) and its hepatic expression with the severity of liver damage in a population of MOPs with NAFLD undergoing bariatric surgery. PCSK9 mRNA was positively correlated with FASN, PPARγ and PPARα mRNAs, while no significant differe…

Clinical anatomic, immunomorphologic and molecular anatomic data suggest interplay of thyroidal molecules, autoantibodies and Hsp60 in Hashimoto’s di…

2014

Hsp60 is, typically, a mitochondrial protein, but it also occurs in the cytosol, vesicles, and plasma membrane, and in the intercellular space and biological fluids, e.g., blood. Changes in the levels and distribution of Hsp60 are linked to several pathologies, including cancer and chronic inflammatory and autoimmune disorders. What is the histopathological pattern of Hsp60 in the thyroid of Hashimoto’s patients? Are there indications of a pathogenic role of Hsp60 that may make Hashimoto’s thyroiditis a chaperonopathy? Experiments reported here provide information regarding those questions. We found by various immunomorphological techniques increased levels of Hsp60 in the thyroid from HT p…

Combination treatment with celecoxib and DHMEQ or curcumin results in synergistic cell growth inhibition in hepatic cancer cells

2007

Thyroid function and release of thyroid-stimulating hormone and prolactin from the pituitary in human obesity

1991

Thyroid function, basal serum thyroid-stimulating hormone (TSH) and prolactin concentrations, and the effects of 200 micrograms TSH-releasing hormone (TRH) given intravenously on TSH (delta TSH) and prolactin (delta prolactin) were investigated in 25 euthyroid obese subjects and 20 lean controls. No significant differences in serum thyroid hormone concentrations, glucose metabolism parameters, or basal TSH and prolactin concentrations were detected between groups, but a significant (P less than 0.01) increase in delta TSH and a significant (P less than 0.01) decrease in delta prolactin were observed in obese subjects. No significant differences in basal TSH and prolactin were observed in ob…

An overview of statin-induced myopathy and perspectives for the future

2020

Introduction: Statins remain the most commonly prescribed lipid-lowering drug class for the treatment of atherosclerotic cardiovascular disease. Their well-recognized side effects are known as statin-associated muscle symptom (SAMS). Some advances in this field have been made in recent years, but the understanding of the mechanisms has lagged. Investigating the specific role of the anti-HMGCR autoantibody, pharmacokinetic genetic variants, characterization of the known phenotypes of statin toxicity, in relation to clinical markers of disease, is of high importance. Areas covered: We summarized currently available findings (on PubMed) related to SAMS and discussed the therapeutic approaches,…

Ihnibitor of Apoptosis Proteins (IAPs) as a new possible therapeutic targets in hepatocellular cancer.

2004

New landscapes and horizons in hepatocellular carcinoma therapy

2020

Hepatocellular carcinoma (HCC), is the sixth most frequent form of cancer and leads to the fourth highest number of deaths each year. HCC results from a combination of environmental factors and aging as there are driver mutations at oncogenes which occur during aging. Most of HCCs are diagnosed at advanced stage preventing curative therapies. Treatment in advanced stage is a challenging and pressing problem, and novel and well-tolerated therapies are urgently needed. We will discuss further advances beyond sorafenib that target additional signaling pathways and immune checkpoint proteins. The scenario of possible systemic therapies for patients with advanced HCC has changed dramatically in …

Management of liver failure: from transplantation to cell-based therapy

2011

The severe shortage of deceased donor organs has driven a search for alternative methods of treating liver failure. In this context, cell-based regenerative medicine is emerging as a promising interdisciplinary field of tissue repair and restoration, able to contribute to improving health in a minimally invasive fashion. Several cell types have allowed long-term survival in experimental models of liver injury, but their therapeutic potential in humans should be regarded with deep caution, because few clinical trials are currently available and the number of patients enrolled so far is too small to assess benefits versus risks. This review summarizes the current literature on the physiologi…

Gestational diabetes and the metabolic syndrome: Can obesity and small, dense low density lipoproteins be key mediators of this association?

2013

Gestational diabetes mellitus (GDM) represents a condition of glucose intolerance with first appearance or recognition at the time of a pregnancy, associated with an inadequate pancreatic response to the advanced insulin resistance of the later stages of pregnancy, and accompanied by enhancing β-cell mass and secretion of insulin. Women who had GDM exhibit a higher risk for later advent of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). Additionally, previous GDM has been proposed as independently correlated with higher risk for development of atherosclerosis in a healthy population, similar to the metabolic syndrome (MetS) and independently of the presence of established…

Frequent Alteration of the Yin Yang 1/Raf-1 Kinase Inhibitory Protein Ratio in Hepatocellular Carcinoma

2011

The transcription factor Yin Yang 1 (YY1) can favor several aspects of tumorigenesis. In turn, Raf-1 Kinase Inhibitor Protein (RKIP) inhibits the oncogenic activities of MAPK and NF-κB pathways and promotes drug-induced apoptosis. Mutual influences between YY1 and RKIP may exist, and there are already separate evidences that relevant increases in YY1 and reductions in RKIP occur in hepatocellular carcinoma (HCC). However, the levels of the two factors have never been concomitantly examined in HCC. We evaluated by RT-PCR the mRNA levels of YY1, YY1AP, RKIP, and survivin in 35 clinical HCCs (91% HCV-related), in their adjacent cirrhotic tissues and in 6 healthy livers. Immunohistochemical ana…

NUPR1, a new target in liver cancer: implication in controlling cell growth, migration, invasion and sorafenib resistance

2016

AbstractSorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced hepatocellular carcinoma (HCC). However, its benefits are modest, and as its mechanisms of action remain elusive, a better understanding of its anticancer effects is needed. Based on our previous study results, we investigated here the implication of the nuclear protein 1 (NUPR1) in HCC and its role in sorafenib treatment. NUPR1 is a stress-inducible protein that is overexpressed in various malignancies, but its role in HCC is not yet fully understood. We found that NUPR1 expression was significantly higher in primary human HCC samples than in the normal liver. Knockdown of NUPR1 signi…

Ecocardiografia transesofagea ed endocardite infettiva.

2008

Gli effetti extraglicemici di liraglutide: Focus sui marker cardiometabolici

2016

The purpose of innovative therapeutic approaches for type 2 diabetes mellitus is to customize the antidiabetic treatment to each patient's need, in order to intensify glucose-lowering effects without hypoglycemia, reduce adverse events, and prevent cardiovascular events. Glucagon-like peptide 1 (GLP-1) analogues are effective drugs in the treatment of type 2 diabetes, and they also seem to have beneficial effects on several risk factors for cardiovascular disease, leading to cardiovascular risk reduction independent of hypoglycemic effects. Among these new drugs, liraglutide, a GLP-1 analogue with a homology of 97% to native GLP-1, exerts an effect on body weight, lipid parameters, blood pr…

Altered gene expression profiles in liver cancer cells upon sorafenib treatment

2010

Diagnosis of focal nodular hyperplasia. Role of imaging techniques.

2002

Focal nodular hyperplasia (FNH) is a rare benign liver lesion which is difficult to differentiate from other benign liver pathologies and hepatocellular carcinoma. However, with appropriate new imaging techniques it is, at present, possible to diagnose this lesion with certainty thus avoiding invasive tests. Patient follow-up is also facilitated. It is often incidentally discovered during an abdominal ultrasound for other pathologies. Color power Doppler allows, in most cases, one to distinguish it from other focal liver lesions. However, in doubtful cases contrast-enhanced computed tomography and magnetic resonance imaging can help us to define the exact nature of the lesion. It is only oc…

Potential Uses of Olive Oil Secoiridoids for the Prevention and Treatment of Cancer: A Narrative Review of Preclinical Studies

2021

The Mediterranean diet (MD) is a combination of foods mainly rich in antioxidants and anti-inflammatory nutrients that have been shown to have many health-enhancing effects. Extra-virgin olive oil (EVOO) is an important component of the MD. The importance of EVOO can be attributed to phenolic compounds, represented by phenolic alcohols, hydroxytyrosol, and tyrosol, and to secoiridoids, which include oleocanthal, oleacein, oleuropein, and ligstroside (along with the aglycone and glycosidic derivatives of the latter two). Each secoiridoid has been studied and characterized, and their effects on human health have been documented by several studies. Secoiridoids have antioxidant, anti-inflammat…

Prostaglandin E2 receptors and COX enxymes in human hepatocellular carcinoma: role in the regulation of cell growth

2008

The aim of this study was to investigate the expression of prostaglandin E 2 receptors (EP 1-4 ), cyclooxygenase-1 (COX-1), and COX-2 in nontumor and tumor human liver tissues, and also to evaluate the antitumor activity of selective EP 1 receptor antagonist used alone or in combination with COX-1 and COX-2 selective inhibitors. Semiquantitative PCR analyses revealed that EP 1-4 , COX-1, and COX-2 mRNA expression was detected in nearly all the tissue samples assayed, although with a high variability between nontumor and tumor tissues. In vitro EP 1 receptor antagonist inhibited anchorage-independent cell growth and reduced the viability of hepatocellular carcinoma (HCC) cells in a dose-depe…

Affidabilità del bright liver nella steatosi epatica in soggetti con ipertransaminasemia criptogenetica e con epatopatia da virus C

2008

Effects of Liraglutide on Carotid Intima-Media Thickness in Patients with Type-2 Diabetes and Non-Alcoholic Fatty Liver Disease: An 8-Month Prospecti…

2014

Sex hormones and risk of liver tumor.

2007

The liver is morphologically and functionally modulated by sex hormones. Long-term use of oral contraceptives (OCs) and anabolic androgenic steroids (AASs) can induce both benign (hemangioma, adenoma, and focal nodular hyperplasia [FNH]) and malignant (hepatocellular carcinoma [HCC]) hepatocellular tumors. Hepatic adenomas (HAs) are rare, benign neoplasms usually occurring in young women, the development and the complications of which have been related to the strength of OCs and the duration of their use. HA incidence has fallen since the introduction of pills containing smaller amounts of estrogens. FNH is a benign lesion, most commonly seen in young women, which is thought to represent a …

PREVALENCE OF HEPATIC STEATOSIS AND ITS RELATIONSHIP WITH CARDIOVASCULAR RISK IN HIV-PATIENTS WITH OR WITHOUT HCV CO-INFECTION

2012

Assunzione di calcio e fattori di rischio comportamentali per la perdita di massa ossea in soggetti con o senza infezione da HIV residenti in un'area…

2012

Long-lasting remission of primary hepatic lymphoma and hepatitis C virus infection achieved by the alpha-interferon treatment

2004

Primary hepatic lymphoma is a rare but well-defined lymphoma entity that often pursues an aggressive clinical course. Most cases have been described in hepatitis C virus (HCV)-related chronic liver disease patients. Although anthracycline-based chemotherapy has been reported to be highly effective, the best therapeutic strategy has not been defined yet. The prognosis is dismal especially in patients treated with chemotherapy alone or when an advanced liver disease is present. Herein, we describe a case of primary hepatic large B-cell non-Hodgkin’s lymphoma, in a patient with HCV chronic infection. After a minor response with eight cycles of CHOP chemotherapy, a complete and sustained remiss…

Down-regulation of wild-type β-catenin expression by interleukin 6 in human hepatocarcinoma HepG2 and leukemia HL60 cells: a possible role in the gro…

2000

Individualized treatment duration for hepatitis C genotype 1 patients: a randomized controlled trial

2008

It was hypothesized that in hepatitis C virus (HCV) genotype 1 patients, variable treatment duration individualized by first undetectable HCV RNA is as effective as standard 48-week treatment. Patients (n_696) received peginterferon alfa-2a, 180 mg/week, or peginterferon alfa-2b, 1.5 mg/kg/week, plus ribavirin, 1000-1200 mg/day, for 48 weeks (standard, n _237) or for 24, 48, or 72 weeks if HCV-RNA–negative at weeks 4, 8, or 12, respectively (variable, n _ 459). Sustained virologic response (SVR) was achieved in 45.1% [95% confidence interval (CI) 38.8-51.4] of the patients in the standard group and in 48.8% (CI 44.2-53.3) of the patients in the variable group (P _ 0.37). The percentages of …

Epidemiology of hepatitic C infection in hemodialysis patients of Sicily

2008

Serological, immunomorphological and bioinformatics analyses suggest Hsp60 is involved in Hashimoto’s thyroiditis pathogenesis.

2013

Micro-RNA segnature of human hepatocellular carcinoma

2008

Platelet changes in patients with hepatitis C virus-related liver cirrhosis after directly acting antiviral therapy

2017

Background and Purpose of the study:Thrombocytopenia is the most common haematological abnormality in patients with Liver Cirrhosis and it is caused by multiple factors. This study evaluated platelets (PLT) count changes in patients with HCV related LC after DAAs therapy. Materials and Methods: We enrolled 83 patients with LC. In all patients were evaluated liver function tests and PLT count at baseline (BL), at end of therapy (ET) and three months post treatment (PostT), Elastography and ultrasound (US) at BL, and US at PostT. LC diagnosis was histological in 13 patients, in 71 with liver stiffness &gt;12 kPa. All patients were SVR (58 patients had DAAs therapy without, 25 with Ribavirin).…

Thrombin-antithrombin III complexes in type II diabetes mellitus.

1992

Several studies suggest that diabetes is associated with a hypercoagulable state. Therefore determination of thrombin-antithrombin complex (TAT) could represent a sensitive parameter for specific detection of a latent activation of the clotting system. The present study documents increased plasma TAT in a heterogeneous group of non-insulin-dependent diabetic patients. The finding of increased TAT levels both in diabetic patients with vascular complications and in vascular disease patients without diabetes suggests a relationship between existing vascular disease and the hemostatic mechanism that produces augmented thrombin activity. In acute vascular occlusions the presence of diabetes seem…

Steatosi epatica (SE) e rischio cardiovascolare in una popolazione di pazienti HIV-positivi

2011

Influence of MEK/ERK signaling on apoptosis induced by selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors in human hepatocellular carcinoma c…

2006

Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways.

2011

Chemotherapy remains a commonly used therapeutic approach for many cancers. Indeed chemotherapy is relatively effective for treatment of certain cancers and it may be the only therapy (besides radiotherapy) that is appropriate for certain cancers. However, a common problem with chemotherapy is the development of drug resistance. Many studies on the mechanisms of drug resistance concentrated on the expression of membrane transporters and how they could be aberrantly regulated in drug resistant cells. Attempts were made to isolate specific inhibitors which could be used to treat drug resistant patients. Unfortunately most of these drug transporter inhibitors have not proven effective for ther…

Targeted therapy for hepatocellular carcinoma: novel agents on the horizon.

2012

Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for 90% of primary liver cancers. In the last decade it has become one of the most frequently occurring tumors worldwide and is also considered to be the most lethal of the cancer systems, accounting for approximately one third of all malignancies. Although the clinical diagnosis and management of early-stage HCC has improved significantly, HCC prognosis is still extremely poor. Furthermore, advanced HCC is a highly aggressive tumor with a poor or no response to common therapies. Therefore, new effective and well-tolerated therapy strategies are urgently needed. Targeted therapies have entered the field of anti-neopl…

Basi fisiopatologiche dell'encefalopatia minima del cirrotico

2006

Glycemic homeostasis in chronic viral hepatitis and liver cirrhosis

2001

Cow's milk–protein allergy as a cause of anal fistula and fissures: A case report

1998

The amplified ELISA assay results correlate well with the standard ELISA results reported previously from our laboratory. Previously it has been necessary to use high flow samplers or long sampling times to measure airborne Fel d 1 concentrations in the range reported here.5 The amplified assay might allow measurements with very short sampling periods to better describe dose-response relationships, and may also be applied to measure airborne concentrations of allergens such as cockroach or dust mite that are airborne at very low concentrations. Our finding that Fel d 1 allergen is measurable in all samples from homes without cats confirms the ubiquitous nature of cat allergen and may help t…

Influence of MEK/ERK signaling on apoptosis induced by selective COX-1 and COX-2 inhibitors in human hepatocellular carcinoma cells

2006

Evaluation of CD1a polymorphism frequencies in patients with pancreatic cancer

2007

Targeting GSK3 and Associated Signaling Pathways Involved in Cancer

2020

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine (S/T) protein kinase. Although GSK-3 originally was identified to have functions in regulation of glycogen synthase, it was subsequently determined to have roles in multiple normal biochemical processes as well as various disease conditions. GSK-3 is sometimes referred to as a moonlighting protein due to the multiple substrates and processes which it controls. Frequently, when GSK-3 phosphorylates proteins, they are targeted for degradation. GSK-3 is often considered a component of the PI3K/PTEN/AKT/GSK-3/mTORC1 pathway as GSK-3 is frequently phosphorylated by AKT which regulates its inactivation. AKT is often active in human cancer a…

Statins and new-onset diabetes

2013

Statins are highly efficacious lipid modifying agents that reduce the risk for cardiovascular (CV) events in both primary and secondary prevention settings. However, statins affect molecular mechanisms which adversely impact on insulin sensitivity and β-cell function, thereby increasing risk for new onset diabetes mellitus (NOD). Defining the mechanisms involved is the focus of considerable current investigation. The statins reduce the risk for CV events in normoglycemic patients as well as in those with diabetes mellitus (DM) and their benefits outweigh the risk of inducing NOD. We review the clinical evidence for NOD with statin treatment, as well as the potential mechanisms involved. Our…

Epatopatie diffuse

2007

Liver disease severity and low bone mineral density in HIV mono-infected and HIV/HCV co-infected patients

2014

Background: In this study we assess: prevalence of osteopenia, osteoporosis and reduced bone mineral density in HIV infection and HIV / HCV co-infection;risk factors associated with reduced bone mineral density(BMD); relationship between bone mineral density and reduced liver fibrosis (FE) measured as "liver stiffness" (LS), by FibroScan ® in patients co-infected with HIV / HCV; relationship between reduced bone mineral density and cardiovascular risk assessed with the 10-year Framingham risk score (FRS) in HIV / HCV co-infected Patients And Methods: One hundred and ninety-four HIV-infected subjects (121 males =62% and 73 females = 38 %): 129 HIV-infected ( 66.5 % ) and 65 HIV / HCV co-infe…

Diagnosis of hepatocellular carcinoma (HCC) is better if early in any case.

2011

Altered Yin Yang 1/RAF-1 kinase inhibitory protein ratio as a possible molecular marker and therapeutic target in hepatocellular carcinoma

2010

Lactose Intolerance and Self-Reported Milk Intolerance: Relationship with Lactose Maldigestion and Nutrient Intake

1998

Background: The relationship between lactose-maldigestion, self-reported milk intolerance and gastrointestinal symptoms has not been clearly defined.Objectives: To evaluate: a) the prevalence of lactose maldigestion and lactose intolerance in a sample of the general population taken from a rural center; b) the frequency of self-reported milk-intolerance and its correlation with lactose-maldigestion; c) the influence of lactose maldigestion, lactose intolerance and self-reported milk intolerance on dietary habits and consumption of total calories, protein, and calcium.Subjects: We studied a randomized sample of the general population in a small center in Sicily. 323 subjects (150 males, 173 …

Subclinical cardiovascular damage in patients with HCV cirrhosis before and after treatment with direct antiviral agents: a prospective study

2018

BACKGROUND Cirrhosis is associated with morpho-functional cardiovascular alterations. AIMS To detect early features of cardiovascular damage in HCV-compensated cirrhotic patients using myocardial deformation indices and carotid arterial stiffness, and, further, to evaluate their short-term behaviour after HCV eradication with direct antiviral agents (DAAs). METHODS Thirty-nine consecutive patients with HCV cirrhosis, without previous cardiovascular events, were studied and matched for age, gender and cardiovascular risk factors to 39 controls without liver or cardiovascular disease. Patients and controls underwent a baseline echocardiographic evaluation including global longitudinal strain …

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy.

2016

Various, diverse molecules contribute to the tumor microenvironment and influence invasion and metastasis. In this review, the roles of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) in the tumor microenvironment and sensitivity to therapy will be discussed. The lipocalin family of proteins has many important functions. For example when NGAL forms a complex with MMP-9 it increases its stability which is important in cancer metastasis. Small hydrophobic molecules are bound by NGAL which can alter their entry into and efflux from cells. Iron transport and storage are also influenced by NGAL activity. Regulation of iron levels is important for survival…

Percutaneous liver biopsy: a safe outpatient procedure?

2001

Following the discovery of hepatitis C virus, more liver biopsies (LB) than before are being performed to assess the severity of liver disease. In this study, following the recommendations for outpatient LB made by the Patient Care Committee of the American Gastroenterological Association, we assessed the feasibility and benefits of LB performed as an outpatient versus inpatient procedure over the last 7 years in our centre. The study included 1,581 patients consecutively examined in our institute; all LBs were performed by a single operator with a 16-gauge needle using the Menghini technique, and in all cases the puncture site was determined using prebiopsy ultrasound. Liver lesions were c…

Associated Factors and Liver Disease Severity for Decreased Bone Mineral Density in HIV Mono- and HIV/HCV Co-infected Patients

2015

Objective: We assessed the prevalence and risk factors of decreased bone mineral density (BMD) in patients mono-infected with human immunodeficiency virus (HIV) or co-infected with hepatitis C virus (HIV/HCV). We also evaluated whether bone loss was linked to lipid asset in both groups and to severity of liver fibrosis in the co-infected group. Methods: We consecutively enrolled 194 HIV-patients (129 mono-infected and 65 co-infected). All HIV-patients underwent dual-energy X-ray absorptiometry (DXA), while co-infected patients underwent transient elastography. Advanced liver fibrosis was defined as a median liver stiffness ≥ 9.5 kPa. Fibrosis was also assessed in all the HIV-patients using …

Progressive visceral leishmaniasis misdiagnosed as cirrhosis of the liver: a case report

2009

Abstract Introduction Visceral leishmaniasis is a potentially life-threatening infectious disease which is caused by parasites of the genus Leishmania and characterized in most cases by the presence of fever as well as signs and symptoms similar to those found in liver cirrhosis. Case presentation In this case report we describe the history of a 50-year-old Caucasian man incorrectly diagnosed as having hepatitis C virus-associated liver cirrhosis, with a massive weight loss of around 100 kg during the previous 2 years. However, suspecting a lymphoproliferative disorder, we were able to make a correct diagnosis of visceral leishmaniasis by bone marrow examination. After a course of therapy w…

Expression of IAPs (Inhibitory of Apoptosis Proteins) and of their alternative splice variants in hepatocellular carcinoma tissues and cells

2004

IAPs (inhibitors of apoptosis proteins) might have a major role in the apoptotic resistance that marks many cancers. The studies on IAPs in human HCC have focused on survivin or XIAP, indicating that their new or increased expression in this tumor is associated with a more unfavorable prognosis. The present results corroborate these findings, emphasizing the role that the coordinated expression of different IAPs and alternative splice variants might play in the adverse biology of hepatocellular carcinoma.

Circulating intercellular adhesion molecule-1 in chronic hepatitis C patients with normal or elevated aminotransferase before and after alpha-interfe…

2001

&lt;i&gt;Objectives:&lt;/i&gt; Intercellular adhesion molecule-1 (ICAM-1) plays a fundamental role during liver inflammation. In fact, weak ICAM-1 expression is physiologically restricted to the endothelium of portal vessels and to sinusoidal lining cells, but it becomes markedly evident on sinusoidal lining cells and at the surface of hepatocytes during inflammatory liver diseases. The aim of this study was to evaluate the behaviour of soluble ICAM-1 (sICAM-1) in chronic hepatitis C (CH-C) patients with persistently normal aminotransferase in comparison with patients with CH-C and elevated aminotransferase, and its changes during α-interferon (IFN) therapy. Immunohistochemical localization…

Roles of GSK-3 and microRNAs on epithelial mesenchymal transition and cancer stem cells.

2017

// James A. McCubrey 1 , Timothy L. Fitzgerald 2 , Li V. Yang 3 , Kvin Lertpiriyapong 4 , Linda S. Steelman 1 , Stephen L. Abrams 1 , Giuseppe Montalto 5,6 , Melchiorre Cervello 6 , Luca M. Neri 7 , Lucio Cocco 8 , Alberto M. Martelli 8 , Piotr Laidler 9 , Joanna Dulinska-Litewka 9 , Dariusz Rakus 10 , Agnieszka Gizak 10 , Ferdinando Nicoletti 11 , Luca Falzone 11 , Saverio Candido 11 and Massimo Libra 11 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA 2 Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC, USA 3 Department of Internal Medicine, Hematology/Oncology Section, Brody Sc…

Rsponse to antiviral therapy and hepatic expression of cycloossogenases in chronic hepatitis C.

2006

Immunologic and absorptive tests in celiac disease: can they replace intestinal biopsies?

1993

The sensitivity and specificity of several immunologic and absorption tests were determined in infants with celiac disease (31 male, 39 female; median age, 2.6 years) in different phases of the disease and in a group of control subjects with chronic diarrhea of different etiologies (32 male, 28 female; median age, 1.2 years). Intestinal biopsy was performed both in the patients and in the controls as a 'gold standard' for the diagnosis. The anti-gliadin antibody (AGA) IgG values showed a sensitivity of 89% and a specificity of 47%; AGA IgA were 69% sensitive and 92% specific; anti-endomysial antibodies (EmA) were 100% sensitive and 97% specific; the xylose test was 71% sensitive and 53% spe…

In vivo triglyceride synthesis in subcutaneous adipose tissue of humans correlates with plasma HDL parameters

2016

Backgrounds and aims: Low concentrations of plasma HDL-C are associated with the development of atherosclerotic cardiovascular diseases and type 2 diabetes. Here we aimed to explore the relationship between the in vivo fractional synthesis of triglycerides (fTG) in subcutaneous (s.q.) abdominal adipose tissue (AT), HDL-C concentrations and HDL particle size composition in non-diabetic humans. Methods: The fTG in s.q. abdominal AT was measured in 16 non-diabetic volunteers (7 women, 9 men; Age: 49 ± 20 years; BMI: 31 ± 5 kg/m; Fasting Plasma Glucose: 90 ± 10 mg/dl) after 2H2O labeling. HDL-C concentration and subclasses, large (L-HDL), intermediate (I-HDL) and small (S-HDL) were measured. Re…

Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: Rationale and importance to inhibiting these pathways in human health

2011

William H. Chappell 1 , Linda S. Steelman 1,2 , Jacquelyn M. Long 2 , Ruth C. Kempf 2 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Jorg Basecke 3 , Franca Stivala 4 , Marco Donia 4 , Paolo Fagone 4 , Graziella Malaponte 4 , Maria C. Mazzarino 4 , Ferdinando Nicoletti 4 , Massimo Libra 4 , Danijela Maksimovic-Ivanic 5 , Sanja Mijatovic 5 , Giuseppe Montalto 6 , Melchiorre Cervello 7 , Piotr Laidler 8 , Michele Milella 9 , Agostino Tafuri 10 , Antonio Bonati 11 , Camilla Evangelisti 12 , Lucio Cocco 12 , Alberto M. Martelli 12,13 , and James A. McCubrey 1 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University 2 Department of Physics, Greenville, N…

Prevalence and risk factors for advanced liver fibrosis in HIV/HCV-coinfected individuals

2010

Non-glycemic effects of pioglitazone and incretin-based therapies.

2013

Atherosclerosis and cardiovascular events are highly prevalent and represent the major cause of mortality in patients with type 2 diabetes. Therefore, there is significant interest in the non-glycemic properties of anti-diabetic agents, particularly on those that are effective on cardiovascular risk factors. Thiazolidinediones and incretin-based therapies (IBTs) represent some of the most recent treatment options approved for the management of type 2 diabetes; these agents have shown important glycemic effects, as well as a number of non-glycemic effects. The latter include those on body weight, inflammation, hypertension and dyslipidemia, thus impacting the different components of the meta…

Yin Yang 1 and raf-1 Kinase Inhibitory Protein Status in Hepatocellular carcinoma: Future Perspectives

2010

We focus on to the role of the transcription factors NF-κB and Yin Yang 1 (YY1) and of Raf-1 kinase inhibitory protein (RKIP) in hepatocellular carcinoma (HCC). YY1, whose expression is enhanced by NF-κB, favors tumorigenesis. RKIP inhibits the oncogenic activities of MAPK and NF-κB pathways and promotes drug-induced apoptosis. Mutual influences between YY1 and RKIP may exist and there is separate evidence that relevant increases in YY1 and reductions in RKIP occur in HCC. In a recent study on clinical HCC, we found that, indeed, the ratio of YY1 to RKIP mRNA and protein expression is very frequently profoundly inverted in tumors compared with adjacent tissues. Hyperactivation of YY1 in tum…

Treatment of giardiasis reverses "active" coeliac disease to "latent" coeliac disease.

2001

In patients with coeliac disease, a regression of intestinal damage without a gluten-free diet is a very rare event. We describe a young child with diarrhoea, intestinal mucosa atrophy and positive serum anti-endomysial and anti-tissue transglutaminase (anti-tTG) antibodies during intestinal giardiasis infection. He showed normal intestinal mucosa architecture and negative anti-endomysial and anti-tTG antibodies after his giardiasis was cured, although he continued to assume a normal diet. Re-evaluations on a 6-monthly basis showed that he was symptom free, and all haemato-chemical parameters were within normal limits. Three years after the initial diagnosis, a third intestinal biopsy showe…

Serum pancreatic enzymes in human immunodeficiency virus-infected children - A collaborative study of the Italian Society of Pediatric Gastroenterolo…

1998

Numerous studies have shown pancreatic disease in adult human immunodeficiency virus (HIV)-infected patients, but there are very few reports on pediatric patients. Our aim was to determine the prevalence of increased serum pancreatic enzyme levels and their relationship to clinical manifestations of acute pancreatitis in HIV-infected children.Forty-seven consecutive, symptomatic HIV-infected children (24 male; median age, 7.3 years; range, 1-17 years) and 45 sex- and age-matched controls without gastroenterologic disease were enrolled. In all subjects serum total amylase, pancreatic amylase, and lipase were assayed with commercial kits. The following were recorded: disease progression (CDC …

Assessment of a qualitative serological assay to screen for allergic sensitization in elderly subjects

2013

We used a commercially available specific IgE qualitative serological assay to screen for allergic sensitization. Two hundred twenty-eight elderly subjects took part in the study. Skin-prick tests (SPTs) to a panel of relevant aeroallergens present in the study area were used as the diagnostic reference procedure (gold standard). Subjects with at least one positive SPT (≥3 mml n = 76) were considered to have developed an allergic sensitization. The qualitative assay correctly classified subjects as sensitized to an allergen or not sensitized in 257 of 288 cases (accuracy, 88.9%; 95% CI, 85.0-92.0%). The qualitative assay sensitivity was 70.0 (95% CI, 58.1-79.7) and specificity was 95.7 (95%…

Hepatic expression of cycloxygenase-2 in non-alcoholic fatty liver disease

2008

The novel NF-κB inhibitor DHMEQ synergizes with celecoxib to exert antitumor effects on human liver cancer cells by a ROS-dependent mechanism

2012

In a previous work of ours dehydroxymethyl-epoxyquinomicin (DHMEQ), an inhibitor of NF-κB, was shown to induce apoptosis through Reactive Oxygen Species (ROS) production in hepatoma cells. The present study demonstrated that DHMEQ cooperates with Celecoxib (CLX) to decrease NF-κB DNA binding and to inhibit cell growth and proliferation more effectively than treatment with these single agents alone in the hepatoma cell lines HA22T/VGH and Huh-6. ROS production induced by the DHMEQ-CLX combination in turn generated the expression of genes involved in endoplasmic reticulum (ER) stress and silencing TRB3 mRNA significantly decreased DHMEQ-CLX-induced cell growth inhibition. Moreover, the DHMEQ-…

Secretin—cerulein test and fecal chymotrypsin concentration in children with intestinal giardiasis

1993

We studied six patients with giardiasis (five males, one female), median age 3.5 yr (range 1-11) and 12 healthy control subjects (10 males, 2 females), median age 3.5 yr (range 1-10). Intestinal biopsy and a contemporaneous secretin-cerulein test were performed in all patients, and fecal chymotrypsin was also assayed. Intestinal biopsy was normal in five of the six patients with giardiasis, whereas one of the six presented a partial atrophy of the intestinal villi. The secretin-cerulein test (1 CU/kg of secretin + 75 ng/kg of cerulein) did not show any significant difference between values in the outputs of chymotrypsin, lipase, phospholipase, and bicarbonate obtained in patients and in con…

Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

2013

Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in t…

Individualized treatment with combination of Peg-interferon alpha 2b and ribavirin in patients infected with HCV genotype 3.

2010

The benefit of individualizing treatment for patients with genotype 3 HCV infection on the basis of viral clearance at week 4 (wk4-R) has not been firmly established.Four hundred and fourteen patients received Peg-interferon alpha-2b plus 1000-1200 mg of ribavirin daily according with body weightor75 kg. Patients were randomized to standard 24 weeks (Std24) or to a 12 or 36 weeks variable treatment duration (Var12/36). In the variable treatment arm, patients with or without wk4-R were allocated to either 12 or 36 weeks duration.At treatment week 4, HCV RNA was undetectable in 262 patients (63.3%), 136 in the Std24, and 126 in the Var12/36 group (p=0.41). In patients with wk4-R, end-of-treat…

Solitary Necrotic Nodule of the Liver: Different Pathological Findings Express a Different Histogenesis

2008

Solitary necrotic nodule of the liver is a rare benign lesion the histogenesis of which is still debated. We here report the case of a patient who underwent laparoscopic cholecystectomy for gallstones and who was accidentally found to have a solitary necrotic nodule of 2 cm in the fifth segment of the liver. On the basis of the histological findings, the hypothesis that different pathogenetic mechanisms could be involved in the histogenesis of this lesion is discussed.

Transcriptional regulation of miR-224 upregulated in human HCCs by NFκB inflammatory pathways

2012

Background & Aims: miR-224 is up-regulated in human HCCs as compared to both paired peri-tumoral cirrhotic tissues and cirrhotic livers without HCC. Here, we have cloned the miR-224 regulatory region and characterized its transcriptional regulation by the NFκB-dependent inflammatory pathways. Methods: Mature miRNA expression was evaluated by a 2 step stem-loop real-time RT-PCR. The recruitment of polymerase II and transcription factors on the pre-miR-224 promoter has been assessed by ChIPSeq and ChIP. Results: We found miR-224 levels strongly up-regulated in both peri-tumoral cirrhotic livers and HCC samples as compared to normal livers. In silico analysis of the putative miR-224 promoter r…

Individualized treatment with combination of Peg-interferon alpha 2b and ribavirin in patients with HCV genotype 3

2010

Background & Aims: The benefit of individualizing treatment for patients with genotype 3 HCV infection on the basis of viral clearance at week 4 (wk4-R) has not been firmly established. Methods: Four hundred and fourteen patients received Peginterferon alpha-2b plus 1000–1200 mg of ribavirin daily according with body weight > or <75 kg. Patients were randomized to standard 24 weeks (Std24) or to a 12 or 36 weeks variable treatment duration (Var12/36). In the variable treatment arm, patients with or without wk4-R were allocated to either 12 or 36 weeks duration. Results: At treatment week 4, HCV RNA was undetectable in 262 patients (63.3%), 136 in the Std24, and 126 in the Var12/36 group (p …

Introduction of WT-TP53 into pancreatic cancer cells alters sensitivity to chemotherapeutic drugs, targeted therapeutics and nutraceuticals

2018

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5–10%. Mutations at the TP53 gene are readily detected in pancreatic tumors isolated from PDAC patients. We have investigated the effects of restoration of wild-type (WT) TP53 activity on the sensitivity of pancreatic cancer cells to: chemotherapy, targeted therapy, as well as, nutraceuticals. Upon introduction of the WT-TP53 gene into the MIA-PaCa-2 pancreatic cancer cell line, the sensitivity to drugs used to treat pancreatic cancer cells such as: gemcitabine, fluorouracil (5FU), cisp…

Serum low density lipoprotein subclasses in asthma

2013

Summary Background The levels of serum low-density lipoproteins (LDL) have been implicated in the inflammatory cascade in a murine model of asthma. Recent findings suggest that LDL may modulate the inflammatory state of the asthmatic airways in humans. Objective We explored whether LDL subclasses are associated with the occurrence and severity of asthma. Methods 24 asthmatics (M/F: 11/13) and 24 healthy individuals, with normal BMI and absence of metabolic syndrome, matched for age and gender. Serum concentrations of LDL subclasses were distributed as seven bands (LDL-1 and -2 defined as large, least pro-inflammatory LDL, and LDL-3 to −7 defined as small, most pro-inflammatory LDL), using t…

Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma.

2006

AIM: To evaluate the immunohistochemical localization of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) on tumor tissue specimens from patients with hepatocellular carcinoma (HCC) and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis (LC) in a group of patients with LC alone and in a control group. METHODS: Three groups of subjects were studied: group I (n = 83) suffering from HCC and LC, group II (n = 72) suffering from LC alone and group III (n = 42) as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the…

Nanotechnology applications for the therapy of liver fibrosis.

2013

Chronic liver diseases represent a major global health problem both for their high prevalence worldwide and, in the more advanced stages, for the limited available curative treatment options. In fact, when lesions of different etiologies chronically affect the liver, triggering the fibrogenesis mechanisms, damage has already occurred and the progression of fibrosis will have a major clinical impact entailing severe complications, expensive treatments and death in end-stage liver disease. Despite significant advances in the understanding of the mechanisms of liver fibrinogenesis, the drugs used in liver fibrosis treatment still have a limited therapeutic effect. Many drugs showing potent ant…

The effects of statins on blood pressure: current knowledge and future perspectives.

2012

Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma

2012

Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5’ and 3’ flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the…

Serological pattern of Hepatitis B, C, and HIV infections among immigrants in Sicily: epidemiological aspects and implication on public health.

2011

The objective of this study was to describe the prevalence of Hepatitis B virus (HBV), Hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections in a cohort of immigrants living in Palermo, Sicily. The study was carried out in the period May 2006-June 2010 and recruited a total of 393 patients (59.8% males-median age of 32.6 years). All patients were tested for serological markers of HBV, HCV, and HIV infection. One-hundred thirty-eight (35.1%) individuals did not show any HBV/HCV/HIV serological marker, while 186 (47.3%) were indicative of past or current HBV infection. A total of 42 (10.7%) subjects were HBsAg positive, 59 (15.0%) showed the serological profile "anti-HBc …

Effects of the MDM-2 inhibitor Nutlin-3a on PDAC cells containing and lacking WT-TP53 on sensitivity to chemotherapy, signal transduction inhibitors …

2019

Abstract Mutations at the TP53 gene are readily detected (approximately 50–75%) in pancreatic ductal adenocarcinoma (PDAC) patients. TP53 was previously thought to be a difficult target as it is often mutated, deleted or inactivated on both chromosomes in certain cancers. In the following study, the effects of restoration of wild-type (WT) TP53 activity on the sensitivities of MIA-PaCa-2 pancreatic cancer cells to the MDM2 inhibitor nutlin-3a in combination with chemotherapy, targeted therapy, as well as, nutraceuticals were examined. Upon introduction of the WT-TP53 gene into MIA-PaCa-2 cells, which contain a TP53 gain of function (GOF) mutation, the sensitivity to the MDM2 inhibitor incre…

Un caso di leishmaniosi viscerale progressiva mascherata da un quadro di cirrosi epatica

2007

Esiste un pattern ecografico associato alla steatosi capace di facilitare il suo riconoscimento etiologico?

2003

Gastroesophageal reflux and cow's milk allergy in infants: A prospective study

1996

Recent reports have suggested that gastroesophageal reflux in pediatric patients may be caused by food allergy.The aim of our study was to determine the frequency of the association of gastroesophageal reflux with cow's milk protein allergy in patients win the first year of life.We studied 204 consecutive patients (median age, 6.3 months) who had been diagnosed as having gastroesophageal reflux on the basis of 24-hour continuous pH monitoring and histologic examination of the esophageal mucosa.Clinical history suggested diagnosis of cow's milk allergy in 19 infants, and 93 others had positive test results (serum IgE anti-lactoglobulin, prick tests, circulating or fecal or nasal mucus eosino…

Cyclooxygenase- 2, Tumor Necrosis Factor-α, Vascular Endothelial Growth Factor-A and IL-6 genes SNPs and IL-6 serum levels in liver cirrhosis and hep…

2011

Production of Anti-Endomysial Antibodies in Cultured Duodenal Mucosa: Usefulness in Coeliac Disease Diagnosis

2002

Although anti-endomysial antibodies (EmA) have been found in the supernatants of cultured intestinal mucosa from patients with coeliac disease (CD), in no study has the clinical reliability of this new diagnostic tool been investigated. Our aims were to evaluate the clinical usefulness of the in vitro production of EmA in CD diagnosis in consecutive patients with suspected CD, and to evaluate the reliability of the in vitro challenge in CD patients on a gluten-free diet (GFD).For the former aim, consecutive patients who were due to undergo intestinal biopsy for suspected diagnosis of CD were enrolled: according to the final diagnosis, these patients were divided into two groups: Group 1 com…

Epidemiology, Diagnosis, and Non-Pharmacological Treatment of HCC

2015

ABSTRACT: Hepatocellular carcinoma (HCC) is still one of the most common tumors, ranking first among all cancers in relation to its frequency and mortality. Only very recently has there been a deceleration in the incidence and mortality of this neoplasia, which suggests that we may be close to the peak of the HCC epidemic, at least in the Western population. Risk factors are well known, and the hepatitis B and hepatitis C viruses are the main etiologic factors. Indeed, liver cirrhosis (LC) of any etiology is the main cause of predisposition to the neoplastic degeneration of the liver; an underlying LC is present in most cases of HCC. For this reason, a surveillance program has been establis…

GSK-3 as potential target for therapeutic intervention in cancer

2014

// James A. McCubrey 1 , Linda S. Steelman 1 , Fred E. Bertrand 2 , Nicole M. Davis 1 , Melissa Sokolosky 1 , Steve L. Abrams 1 , Giuseppe Montalto 3 , Antonino B. D’Assoro 4 , Massimo Libra 5 , Ferdinando Nicoletti 5 , Roberta Maestro 6 , Jorg Basecke 7,8 , Dariusz Rakus 9 , Agnieszka Gizak 9 Zoya Demidenko 10 , Lucio Cocco 11 , Alberto M. Martelli 11 and Melchiorre Cervello 12 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC, USA 2 Department of Oncology, Brody School of Medicine at East Carolina University Greenville, NC, USA 3 Biomedical Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy …

Nutraceuticals as an Important Part of Combination Therapy in Dyslipidaemia

2017

Several risk factors such as abnormality of lipid metabolism (e.g. high levels of low-density lipoprotein cholesterol (LDL-C), elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C)) play a central role in the aetiology of cardiovascular disease (CVD). Nutraceutical combination together with a cholesterol- lowering action, when associated with suitable lifestyle, should furnish an alternative to pharmacotherapy in patients reporting statin-intolerance and in subjects at low cardiovascular risk. The present review is focused on nutraceuticals and their synergetic combinations demonstrating a beneficial effect in the management of dyslipidaemia. Several nutraceu…

The Role of GSK-3 in Cancer Immunotherapy: GSK-3 Inhibitors as a New Frontier in Cancer Treatment

2020

The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified because of its key role in the regulation of glycogen synthesis. However, it is now well-established that GSK-3 performs critical functions in many cellular processes, such as apoptosis, tumor growth, cell invasion, and metastasis. Aberrant GSK-3 activity has been associated with many human diseases, including cancer, highlighting its potential therapeutic relevance as a target for anticancer therapy. Recently, newly emerging data have demonstrated the pivotal role of GSK-3 in the anticancer immune response. In the last few years, many GSK-3 inhibitors have been developed, and some are currently being te…

Effects of Steatosis on Hepatic Hemodynamics in Patients with Metabolic Syndrome

2015

The aim of our study was to assess the hemodynamic changes in hepatic and splenic circulation using B-mode ultrasonography and color Doppler ultrasonography, in a population of patients with metabolic syndrome divided with respect to the presence or absence of steatosis diagnosed by ultrasonography. One hundred forty-one patients were included in the study. The severity of non-alcoholic fatty liver disease was classified as mild, moderate or severe. Visceral fat thickness, longitudinal diameter of the spleen, diameter of the portal vein, mean maximum portal vein flow velocity, hepatic artery and splenic artery resistivity indexes and hepatic vein flow phasicity were measured. Non-alcoholic …

Un caso di Leishmaniosi viscerale progressiva: ruolo del color Doppler nella diagnosi

2008

Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study.

2014

Background Liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) analog, has several non- glycemic properties, but its effect on carotid intima-media thickness (IMT), a recognized marker of subclinical atherosclerosis, is still unknown. Methods A prospective study of 8 months duration in 64 patients with type-2 diabetes and no prior history of coronary artery disease evaluated whether adding liraglutide to metformin affects carotid IMT, measured by color doppler ultrasound. Results After 8 months, fasting glucose decreased by 2.1 mmol/l and HbA1c by 1.9% (p < 0.01 for all). Liraglutide reduced total-cholesterol and triglycerides by 10%, and LDL-cholesterol by 19%, whereas HDL-cholester…

Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238 (ixazomib) in hepatocellular carcinoma cells

2017

AbstractHepatocellular carcinoma (HCC) is one of the common malignancies and is an increasingly important cause of cancer death worldwide. Surgery, chemotherapy, and radiation therapy extend the 5-year survival limit in HCC patients by only 6%. Therefore, there is a need to develop new therapeutic approaches for the treatment of this disease. The orally bioavailable proteasome inhibitor MLN2238 (ixazomib) has been demonstrated to have anticancer activity. In the present study, we investigated the preclinical therapeutic efficacy of MLN2238 in HCC cells through in vitro and in vivo models, and examined its molecular mechanisms of action. MLN2238 inhibited cell viability in human HCC cells He…

Downregulation of wild-type β-catenin expression by interleukin 6 in human hepatocarcinoma HepG2 cells: a possible role in the growth-regulatory effe…

2001

We investigated the antitumour effects of interleukin 6 (IL-6) on hepatocarcinoma HepG2 cells, endowed with high levels of a mutated, non-degradable, beta-catenin. IL-6 produced minimal growth-inhibitory effects and no apoptosis or gross changes in cell adhesion. Interestingly, however, it caused a consistent decrease in the cytoplasmic levels of wild-type, but not of mutated, beta-catenin protein. There was no effect on E-cadherin or gamma-catenin and a reduction in alpha-catenin occurred only at high concentrations. IL-4, a non-related cytokine, did not modify the content of beta-catenin. IL-6 did not influence beta-catenin mRNA levels. LiCl, a potent inhibitor of Glycogen Synthase Kinase…

Nontumorous portal vein thrombosis in liver cirrhosis: Possible role of β-blockers

2018

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; Nonselective β-blockers (NSBB) are used in liver cirrhosis (LC) to prevent variceal bleeding because they decrease portal pressure. A main risk factor for the development of portal vein thrombosis (PVT) in LC is decreased portal vein inflow velocity. The aim of our study was to examine retrospectively the incidence of PVT and its correlation with the use of β-blockers in a cohort of LC patients. &lt;b&gt;&lt;i&gt;Subjects and Methods:&lt;/i&gt;&lt;/b&gt; Data from 230 LC patients (90% Child-Pugh class A), who had been followed up for at least 5 years, were reviewed. The diagnosis of PVT was made by ultrasound. The presence of PVT was evaluate…

A novel beneficial effect of liraglutide: the reduction in subclinical atherosclerosis in patients with type-2 diabetes.

2012

KIR2DL3 and the KIR ligand groups HLA-A-Bw4 and HLA-C2 predict the outcome of hepatitis B virus infection.

2017

Killer immunoglobulin-like receptors (KIRs) regulate the activation of Natural Killer cells through their interaction with human leukocyte antigens (HLA). KIR and HLA loci are highly polymorphic and certain HLA-KIR combinations have been found to protect against viral infections. In this study we analyzed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty-seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection, and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA-A-Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude…

Heat Shock Protein 70 Serum Levels Differ Significantly in Patients with Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma

2014

Members of the heat shock protein 70 (HSP70) family play an important role in assisting protein folding, preventing protein aggregation and transport of proteins across membranes under physiological conditions. Following environmental (i.e., irradiation, chemotherapy), physiological (i.e., cell growth, differentiation), and pathophysiological (i.e., inflammation, tumorigenesis) stress, the synthesis of heat shock proteins (HSPs) is highly up-regulated, whereas protein synthesis in general is reduced. In contrast to normal cells, many tumor entities including hepatocellular carcinoma (HCC) overexpress HSP70, the major-stress-inducible member of the HSP70 family, present it on their cell surf…

Disfunzione endoteliale e malattia carotidea in pazienti con bright liver echopattern

2006

GSK-3? Can Regulate the Sensitivity of MIA-PaCa-2 Pancreatic and MCF-7 Breast Cancer Cells to Chemotherapeutic Drugs, Targeted Therapeutics and Nutra…

2021

Glycogen synthase kinase-3 (GSK-3) is a regulator of signaling pathways. KRas is frequently mutated in pancreatic cancers. The growth of certain pancreatic cancers is KRas-dependent and can be suppressed by GSK-3 inhibitors, documenting a link between KRas and GSK-3. To further elucidate the roles of GSK-3β in drug-resistance, we transfected KRas-dependent MIA-PaCa-2 pancreatic cells with wild-type (WT) and kinase-dead (KD) forms of GSK-3β. Transfection of MIA-PaCa-2 cells with WT-GSK-3β increased their resistance to various chemotherapeutic drugs and certain small molecule inhibitors. Transfection of cells with KD-GSK-3β often increased therapeutic sensitivity. An exception was observed wi…

Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mtor pathways in controlling growth and sensitivity to therapy-implications for cancer and aging

2011

Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described …

Low-grade fever: how to distinguish organic from non-organic forms.

2010

Summary Background and aim:  Low-grade fever (LGF) is defined as a body temperature between 37.5 and 38.3 °C, which is below the classical value reported for fever of unknown origin (FUO). We attempted to characterise its epidemiology, aetiology and clinical aspects to improve the methodological approach to diagnosis. Design and Methods:  We reviewed and evaluated a survey of patients with LGF, followed as outpatients of our Department, a tertiary referral centre from 1997 to 2008. The same classifications were applied for classical FUO, and in the patients diagnosed with LGF, we also investigated for habitual hyperthermia (HH). Results:  Seventy-three patients were selected and divided int…

Variazioni emodinamiche del circolo epatico in pazienti con bright liver ecopattern e sindrome metabolica

2007

Corrigendum to "poly (ADP-ribose) polymerase inhibition synergizes with the NF-κB inhibitor DHMEQ to kill hepatocellular carcinoma cells" [Biochim. B…

2018

Fig. 1. The effects of the DHMEQ–Olaparib combination on HCC cells. (A) Cells were treated for 72 hwith the indicated concentrations of DHMEQ–Olaparib and cell viability was assessed by MTS assays. The DHMEQ–Olaparib combination showed synergistic inhibition of cell viability in Hep3B cells and additive inhibition in Huh7 cells. Combination index (CI) values are indicated above the bar. Data are expressed as percent cell growth and are the mean ± SD of three separate experiments (each of which was performed in triplicate). *p b 0.05 and **p b 0.01 versus each agent alone. (B) Cells were treated for 24 h with DHMEQ (μg/ml) or Olaparib (μM) alone or in combination, allowed to grow for 14 days…

POLYMORPHISMS IN TYPE 1 AND TYPE 2 CYTOKINE GENES MIGHT PLAY COMPLEMENTARY ROLE IN PANCREATIC CANCER SUSCEPTIBILITY.

2007

Le Febbricole.

2008

Ultrasound detection of abdominal lymph nodes in chronic liver diseases. A retrospective analysis

2003

Aim: To retrospectively evaluate the prevalence of lymph nodes of the hepato-duodenal ligament in a group of patients with chronic liver disease of various aetiologies and to investigate what clinical, aetiological and laboratory data may lead to their appearance. Materials and methods: One thousand and three patients (554 men, 449 women) were studied, including 557 with chronic hepatitis and 446 with liver cirrhosis. The presence of lymph nodes near the trunk of the portal vein, hepatic artery, celiac axis, superior mesenteric vein and pancreas head was investigated using ultrasound. Results: Lymph nodes were detected in 394 out of the 1003 study patients (39.3%); their number ranged from …

Waiting-time and quality of care deserved to patients with early stage hepatocellular carcinoma undergoing RFA treatment

2017

Hepatitis C Virus positive patients with persistently normal serum transaminase: a long-term follow-up

2010

Occult Hepatitis B Infection in the Immigrant Population of Sicily, Italy.

2012

In Italy, about 7 % of the resident population is represented by immigrants originating from geographic regions at high endemicity for hepatitis B virus infection. This study aims to assess the prevalence of occult HBV infection (OBI) including the identification of HBV-genotypes in a population of immigrants serologically negative for hepatitis B surface antigen (HBsAg). Between May 2006 and May 2010, 339 immigrants were tested for markers of HBV, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. HBV-DNA was tested by using nested-PCR assays on three different genetic region. HBV-DNA was detected in plasma samples of 11/339 (3.2 %) patients. Most of them had no ser…

Hospital Care of Older Patients With COPD: Adherence to International Guidelines for Use of Inhaled Bronchodilators and Corticosteroids

2019

Abstract Objectives We aimed to analyze the prevalence and impact of COPD in older patients hospitalized in internal medicine or geriatric wards, and to investigate adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, associated clinical factors, and outcomes. Design Data were obtained from REgistro POliterapie SIMI (REPOSI), a prospective multicenter observational registry that enrolls inpatients aged ≥65 years. Setting and Participants Older hospitalized patients enrolled from 2008 to 2016 with a diagnosis of COPD. Measures We evaluated adherence to the 2018 GOLD guidelines at admission and discharge, by examining the prescription of inhaled bronchodi…

SURVEILLANCE PROGRAM FOR DIAGNOSIS OF HCC IN LIVER CIRRHOSIS: ROLE OF ULTRASOUND ECHOPATTERNS

2013

Role of pancreatic impairment in growth recovery during gluten-free diet in childhood celiac disease

1997

Abstract BACKGROUND & AIMS: Clinical significance and duration of insufficient release of pancreatic enzymes in childhood celiac disease have not been clarified. The aim of this study was to evaluate the role that pancreatic impairment plays in growth recovery and the duration of this impairment. METHODS: Forty-six patients with celiac disease who had a median age of 2.5 years were enrolled. Fecal chymotrypsin level was determined at diagnosis and then every 15 days after the beginning of a gluten-free diet in all patients. RESULTS: At diagnosis, 17 of 46 patients with celiac disease had subnormal fecal chymotrypsin values. During the gluten-free diet, a progressive reduction in the percent…

Nodulo epatico ipovascolare: ruolo dell’ecografia nella diagnosi di HCC

2008

Estrogen receptors α (ERα), ERβ and their variants may be responsible for estrogen implication in human liver carcinogenesis and tumor progression

2009

Chronic constipation as a symptom of cow milk allergy

1995

Twenty-seven consecutive infants (mean age, 20.6 months) with chronic "idiopathic" constipation were studied to investigate the possible relation between constipation and cow milk protein allergy (CMPA). The infants were initially observed on an unrestricted diet, and the number of stools per day was recorded. Subsequently the infants were put on a diet free of cow milk protein (CMP) for two periods of 1 month each, separated by two challenges with CMP. During the CMP-free diet, there was a resolution of symptoms in 21 patients; during the two consecutive challenges, constipation reappeared within 48 to 72 hours. In another six patients the CMP-free diet did not lead to improvement of const…

Diagnostic Accuracy of Fecal Calprotectin Assay in Distinguishing Organic Causes of Chronic Diarrhea from Irritable Bowel Syndrome: A Prospective Stu…

2003

AbstractBackground: Fecal calprotectin (FC) has been proposed as a marker of inflammatory bowel disease (IBD), but few studies have evaluated its usefulness in patients with chronic diarrhea of various causes. We evaluated the diagnostic accuracy of a FC assay in identifying “organic” causes of chronic diarrhea in consecutive adults and children.Methods: We consecutively enrolled 70 adult patients (30 males, 40 females; median age, 35 years) and 50 children (20 males, 30 females; median age, 3.5 years) with chronic diarrhea of unknown origin. All patients underwent a complete work-up to identify the causes of chronic diarrhea. FC was measured by ELISA.Results: In adult patients, FC showed 6…

Il bright liver echopattern come strumento diagnostico non invasivo di steatosi nell'ipertransaminasemia criptogenetica

2005

Nutritional characteristics of a rural Southern Italy population: the Ventimiglia di Sicilia Project.

2002

Knowledge of alimentary habits among populations permits a better definition of appropriate public health interventions. We designed the epidemiological project "Ventimiglia di Sicilia" to characterize the risk profile in a rural village with low total cholesterol levels and low early cardiovascular mortality but with a large prevalence of overweight and obesity, which previously have been significantly associated with total mortality.488 individuals of age 20 to 69 years were included in the dietary survey conducted by a seven-day food record.Alimentary habits were characterized by high consumption of total and complex carbohydrates (respectively 52.5 +/- 7.6% and 46.6 +/- 8.2% of daily en…

HLA and killer cell immunoglobulin-like receptors influence the natural course of CMV infection.

2014

Background. Natural killer (NK) cells provide a major defense against cytomegalovirus (CMV) infection through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulinlike receptors (KIRs), and human leukocyte antigens (HLA) class I molecules. This study assessed whether the KIR and HLA repertoire may influence the risk of developing symptomatic or asymptomatic disease after primary CMV infection in the immunocompetent host. Methods. Sixty immunocompetent patients with primary symptomatic CMV infection were genotyped for KIR and their HLA ligands, along with 60 subjects with a previous asymptomatic infection as controls. Results. The frequency…

Pancreatic enzyme therapy in childhood celiac disease. A double-blind prospective randomized study.

1995

The validity of pancreatic enzyme substitution therapy in the two months following diagnosis of celiac disease was investigated. Twenty patients (8 males, 12 females), mean age 14.2 months (group A) received an enzyme substitution preparation. The control group (group B) included 20 patients (9 males, 11 females), mean age 14.5 months, treated with placebo. Before starting treatment, we performed a stratification for age, weight-for-age at diagnosis, and degree of pancreatic insufficiency. The therapies were then administered randomly in double-blind fashion. On diagnosis and 30 and 60 days after commencement of a gluten-free diet with identical calorie intake in both groups, a series of an…

Usefullness of abdominal ultrasound in celiac disease: diagnosis anf follow-up

2006

Le Febbricole.

2008

Randomised trial of two different daily doses of interferon-α versus classical therapy in treatment-naïve patients with chronic hepatitis C

2002

Objective: To evaluate the efficacy and tolerability of two different daily doses of interferon-α (lymphoblastoid-IFNα-N1, Wellferon®) [IFNα] for 2 months, followed by the same dose on alternate days for up to 1 year, versus administration on alternate days for 1 year. Patients and methods: A non-blind, randomised study of outpatients with chronic hepatitis C at five centres in Sicily, Italy. Ninety-seven consecutive treatment-naïve patients [72 patients with hepatitis C virus (HCV) genotype 1b infection] with histological chronic hepatitis C were included in the study and randomised to receive IFNα subcutaneously: 5 million international units (MIU) daily for 2 months, followed by the same…

Diet and Gallstones in Women of a Rural Town of Sicily

1997

To test the possible association between dietary factors and gallstones, we performed a case-control study on the dietary habits of 71 women with gallstones in a rural area of Sicily (mean age 63.2 years) and compared these with 142 women who did not have gallstones (mean age 63.6 years) selected at random from the same general population. The dietary questionnaire, based on data collected over 7 days, was carefully compiled by two dieticians specially trained for the study. The daily calorie intake was higher in the women with gallstones ( p= 0.006) and was equally distributed between fats, carbohydrates and proteins. The intakes of unsaturated fats ( p= 0.03), unrefined sugars ( p= 0.01) …

The Role of Vitamin Deficiency in Liver Disease: To Supplement or Not Supplement?

2021

Over the past few years, growing interest has been shown for the impact of dietary requirements and nutritional factors on chronic diseases. As a result, nutritional programs have been reinforced by public health policies. The precise role of micronutrients in chronic liver disease is currently receiving particular attention since abnormalities in vitamin levels are often detected. At present, treatment programs are focused on correcting vitamin deficiencies, which are frequently correlated to higher rates of comorbidities with poor outcomes. The literature reviewed here indicates that liver diseases are often related to vitamin disorders, due to both liver impairment and abnormal intake. M…

Febbricola persistente.

2008

Association between single nucleotide polymorphysms (SNPs) of IL-6, TNF-alpha and VEGF-A genes and susceptibility to hepatocellular carcinoma (HCC)

2009

Adipokines and lipoproteins: modulation by antihyperglycemic and hypolipidemic agents.

2014

Adipose tissue is an endocrine organ that secretes a number of hormones and metabolically active substances that impact energy metabolism and insulin sensitivity. These inflammatory markers are collectively referred to as adipocytokines, or adipokines. Adipose tissue's functional capacity and metabolic activity vary among individuals, thus partly explaining the incomplete overlap between obesity and the metabolic syndrome. The functional failure of adipose tissues results in changed energy delivery and impaired glucose consumption, triggering self-regulatory mechanisms to maintain homeostasis. Antihyperglycemic, hypolipidemic, antiobesity, and angiotensin II receptor blocker drugs influence…

Hemodynamic changes in splanchnic circulation after orthotopic liver transplantation in patients with liver cirrhosis

2002

Background: Liver cirrhosis increases portal vein pressure and alters the splanchnic circulation. With Doppler sonography, we investigated the hemodynamic changes in the portal vein, superior mesenteric artery, hepatic and splenic arteries and spleen size in a group of patients with end-stage liver disease before and after orthotopic liver transplantation (OLT). Methods: Ten patients (seven male, three female; mean age = 48.8 ± 7.6 years) who underwent OLT for liver cirrhosis mainly associated with hepatitis C virus infection completed the study. The control group consisted of 10 patients matched by sex and age who had no gastroenterologic or vascular diseases. All patients underwent duplex…

Reliability of the bright liver echo pattern in diagnosing steatosis in patients with cryptogenic and HCV-related hypertransaminasaemia.

2008

Aim To evaluate the reliability of the bright liver (BL) echo pattern on ultrasound to detect histological steatosis in chronic cryptogenic hypertransaminasaemia (CCH) and hepatitis C virus (HCV)-related forms of hypertransaminasaemia. Materials and methods One hundred and fifty patients, 54 with CCH and 96 with HCV hypertransaminasaemia (76 genotype 1/2 and 20 genotype 3), were enrolled. Histological steatosis was measured as the percentage of hepatocytes involved. The reliability of the BL sign was estimated using the sensitivity, specificity, positive and negative predictive values. Results Histological steatosis was present in 102/150 patients (68%) divided into 59/96 (62%) in the HCV g…

UN CASO DI TUBERCOLOSI (TBC) DISSEMINATA A PREVALENTE LOCALIZZAZIONE ADDOMINALE: UTILITA' DELL'ECOGRAFIA.

2009

Response to antiviral therapy and hepatic expression of cyclooxygenases in chronic hepatitis C

2007

OBJECTIVES: The aims of this study were to investigate the expression of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) in chronic hepatitis C (CHC) by immunohistochemistry, based on the hypothesis that COXs expression could vary according to genotype, viral load, liver steatosis, BMI and response to therapy and to determine whether the addition of selective COX inhibitors could have a rationale in increasing the efficacy of antiviral therapy. METHODS: We used 35 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle biopsy from patients with CHC (17F/18M) with one of two types of genotype (1b and 3a). The presence of COX-1 and COX-2 in the cytoplasm of hepatocyt…

Significance of Autologous Interleukin-6 Production in the HA22T/VGH Cell Model of Hepatocellular Carcinoma

2006

Cancer cells may often support their own growth, survival, and drug resistance by autocrine/paracrine loops based on the production of different factors; results from us and others have shown that similar interleukin-6 (IL-6)-related loops are operative in multiple myeloma and prostate or renal cancer. Because this aspect has not been investigated in detail for hepatocellular carcinoma (HCC), we have examined it in HA22T/VGH cells. These differ from other primary liver cancer cell lines (that is, HepG2, HuH-6, and HuH-7) in that enzyme-linked immunosorbent assay (ELISA) showed the HA22T/VGH cells to secrete remarkable amounts of IL-6 (16.8 ng/10(6) cells/24 h); this production, due to const…

PERCUTANEOUS RADIOFREQUENCY THERMAL ABLATION 8 RFTA) OF SMALL HEPATOCELLUALR CARCINOMA: A PROSPECTIVE STUDY

2004

PERCUTANEOUS RADIOFREQUENCY THERMAL ABLATION 8 RFTA) OF SMALL HEPATOCELLUALR CARCINOMA: A PROSPECTIVE STUDY Data: 2004 Dettaglio tipologia d'Ateneo: 3a - Articoli su riviste ISI (anche on line)

The selective cyclooxygenase-1 inhibitor SC-560 suppresses cell proliferation and induces apoptosis in human hepatocellular carcinoma cells

2006

Two isoforms of cyclooxygenase (COX) are known, and to date most studies have implicated COX-2 in the development and progression of various human cancers. Increasing evidence suggests that COX-1 may also play a similar role. Indeed, we have recently observed that the dual COX-1/COX-2 inhibitor indomethacin induces apoptosis in human hepatocellular carcinoma (HCC) cell lines more effectively than the selective COX-2 inhibitors, possibly implicating COX-1 in HCC. In this study we investigated the expression of COX-1 in non-tumor and malignant human liver tissues, as well as the effects of the highly selective COX-1 inhibitor SC-560 on cell growth and apoptosis in human HCC cell lines. Expres…

Targeting breast cancer initiating cells: advances in breast cancer research and therapy

2014

Over the past 10 years there have been significant advances in our understanding of breast cancer and the important roles that breast cancer initiating cells (CICs) play in the development and resistance of breast cancer. Breast CICs endowed with self-renewing and tumor-initiating capacities are believed to be responsible for the relapses which often occur after various breast cancer therapies. In this review, we will summarize some of the key developments in breast CICs which will include discussion of some of the key genes implicated: estrogen receptor (. ER), HER2, BRCA1, TP53, PIK3CA, RB, P16INK1 and various miRs as well some drugs which are showing promise in targeting CICs. In additio…

Percutaneous radiofrequency therma ablation of small hepatocellular carcinoma: a prospective study

2004

Targeting NUPR1 with the Small Compound ZZW-115 Is an Efficient Strategy to Treat Hepatocellular Carcinoma

2020

International audience; HCC is a highly lethal malignancy with Sorafenib as the only molecularly targeted drug. The multifunctional stress-associated protein, NUPR1, plays an essential role in controlling cell growth, migration, invasion and Sorafenib resistance in HCC. We report here that NUPR1 expression is absent in healthy liver and it is progressively upregulated in HCC premalignant lesions such as hepatitis and cirrhosis with a maximum expression in HCC samples, highlighting that NUPR1 is a potential drug target for HCC. We therefore assessed in this work, ZZW-115, a strong inhibitor of NUPR1, as a promising candidate for the treatment of HCC. We validated its extraordinary antitumor …

Serum and fecal pancreatic enzymes in beta-thalassemia major

1997

This study, using indirect tests, demonstrated that exocrine pancreatic function is impaired in a proportion of patients with beta-thalassemia major (TM), though this impairment is generally mild or moderate.Impaired structure and function of the exocrine pancreas has been reported in patients with Beta-thalassemia major.In this study we measured fecal fats and serum and fecal pancreatic enzymes in 30 patients (13 M, 17 F) with TM, mean age 22.1 yr (range 14-39) and compared them with those of a matched group of healthy controls. Results were correlated with age, serum ferritin, blood transfusion, and various nutritional parameters. Enzymes assays included: serum pancreatic amylase (PA), li…

The metabolic syndrome and HIV infection.

2013

The metabolic syndrome (MetS), a cluster of risk factors for cardiovascular disease and type 2 diabetes, has become an important public health problem. Considerable differences in the prevalence of the MetS in human immunodeficiency virus (HIV)-infected subjects have been reported, as a consequence of several limitations regarding the diagnostic critera for MetS. New evidence suggests that the use of optimal waist cut-off points specific for the various ethnic populations could represent a step forward in overcoming these limitations. Also the use of specific cut-off points for measuring upper trunk fat as an adjunctive criterion of MetS in HIV patients with lipodystrophy could represent an…

Circulating Levels of Adhesion Molecules in Chronic Kidney Disease Correlate with the Stage of Renal Disease and with C-Reactive Protein

2007

Patients with chronic renal failure (CRF) suffer from a series of complications linked to the atherosclerotic process in which the endothelial dysfunction mediated by the activation of some adhesion molecules plays an important role. This study aims to evaluate circulating levels of intercellular adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecules-1 (VCAM-1) in patients with predialysis CRF, on maintenance hemodialysis (HD) and after kidney transplantation (KTx) and to correlate them with some inflammation and nutritional indexes.Thirty two patients with predialysis CRF, 30 on maintenance HD, 36 after KTx and 28 subjects as a control group (C) were included in this study. Cir…

Himpact of liver steatosis on the antiviral response in the hepatitis C virus –associated chronic hepatitis.

2006

Correlation between soluble adhesion molecules, TNF alpha malnutrition and inflammation in renal patients.

2004

Studio sulla frequenza dei genotipi virali e loro risposta terapeutica su un gruppo di soggetti ex drug dipendents con epatite cronica HCV-correlata.

2006

The association of variants in PNPLA3 and GRP78 and the risk of developing hepatocellular carcinoma in an Italian population

2016

// Daniele Balasus 1, * , Michael Way 2, * , Caterina Fusilli 3 , Tommaso Mazza 3 , Marsha Y. Morgan 2 , Melchiorre Cervello 4 , Lydia Giannitrapani 1 , Maurizio Soresi 1 , Rosalia Agliastro 5 , Manlio Vinciguerra 2, 6 , Giuseppe Montalto 1, 4 1 Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy 2 Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK 3 IRCCS Casa Sollievo della Sofferenza, Bioinformatics Unit, San Giovanni Rotondo (FG), Italy 4 Institute of Biomedicine and Molecular Immunology, National Research Council (C.N.R.), Palermo, Italy 5 Immunohematology and Trans…

A PTEN inhibitor displays preclinical activity against hepatocarcinoma cells

2016

Phosphatase and tensin homolog (PTEN) gene is considered a tumor suppressor gene. However, PTEN mutations rarely occur in hepatocellular carcinoma (HCC), whereas heterozygosity of PTEN, resulting in reduced PTEN expression, has been observed in 32–44% of HCC patients. In the present study, we investigated the effects of the small molecule PTEN inhibitor VO-OHpic in HCC cells. VO-OHpic inhibited cell viability, cell proliferation and colony formation, and induced senescence-associated β-galactosidase activity in Hep3B (low PTEN expression) and to a lesser extent in PLC/PRF/5 (high PTEN expression) cells, but not in PTEN-negative SNU475 cells. VO-OHpic synergistically inhibited cell viability…

Lysosomal cathepsins B and L and Stefin A blood levels in patients with hepatocellular carcinoma and/or liver cirrhosis: potential clinical implicati…

1997

The serum levels of lysosomal cathepsin B and L and Stefin A, an intracellular inhibitor of these proteolytic enzymes, were determined in patients with hepatocellular carcinoma (HCC) and/or liver cirrhosis (LC) and correlated with some clinical and biochemical parameters of these diseases. Cathepsin B serum levels were increased in HCC and in LC patients as compared to normal subjects (p &lt; 0.001). However no difference was observed between HCC and LC groups. Interestingly, a significant relationship was evidenced between cathepsin B serum content and the grade of severity of cirrhosis (r = 0.41; p &lt; 0.001). Cathepsin L was significantly elevated only in sera of cancer patients as comp…

Response to "Is the Reg3α (HIP/PAP) Protein Really an Obesogenic Factor?"

2015

Peer Reviewed

Effect of liraglutide on carotid intima-media thickness in patients with type-2 diabetes: a 4-month prospective study

2012

Common polymorphisms in Th1 and Th2 cytokine genes and susceptibility to pancreatic adenocarcinoma

2006

Circulating levels of molecular adhesion correlate with stage of renal disease and C-reactive protein in chronic kidney disease

2007

BACKGROUND: Patients with chronic renal failure (CRF) suffer from a series of complications linked to the atherosclerotic process in which the endothelial dysfunction mediated by the activation of some adhesion molecules plays an important role. This study aims to evaluate circulating levels of intercellular adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecules-1 (VCAM-1) in patients with predialysis CRF, on maintenance hemodialysis (HD) and after kidney transplantation (KTx) and to correlate them with some inflammation and nutritional indexes. METHODS: Thirty two patients with predialysis CRF, 30 on maintenance HD, 36 after KTx and 28 subjects as a control group (C) were inclu…

Un caso di tubercolosi disseminata con prevalente interessamento addominale associato a sindrome emofagocitica

2009

ASSOCIAZIONE TRA ATEROSCLEROSI CAROTIDEA, DISFUNZIONE ENDOTELIALE E STEATOSI EPATICA IN UNA POPOLAZIONE CON SINDROME METABOLICA.

2007

Novel combination of celecoxib and proteasome inhibitor MG132 provides synergistic antiproliferative and proapoptotic effects in human liver tumor ce…

2010

Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Celecoxib (Celebrex®) exhibits antitumor effects in human HCC cells, and its mechanism of action is mediated either by its ability to inhibit cyclooxygenase 2 (COX-2) or by a number of various other COX-2 independent effects. Proteasome inhibitors (PIs) can exert cell growth inhibitory and apoptotic effects in different tumor cell types, including HCC cells. The present study examined the interaction between celecoxib and the PI MG132 in two human liver tumor cell lines HepG2 and HA22T/VGH. Our data showed that each inhibitor reduced proliferation and induced apoptosis in a dose-dependen…

Un caso di schistosomiasi: utilità dello score ecografico dell'Organizzazione Mondiale della Sanità

2004

Comparison of anti-transglutaminase ELISAs and an anti-endomysial antibody assay in the diagnosis of celiac disease: A prospective study

2002

Abstract Background: Most studies of anti-transglutaminase (anti-tTG) assays have considered preselected groups of patients. This study compared the sensitivity, specificity, and predictive value of an immunofluorescence method for anti-endomysial antibodies (EmAs) and two anti-tTG ELISAs, one using guinea pig tTG (gp-tTG) and the other human tTG (h-tTG) as antigen, in consecutive patients investigated for suspected celiac disease (CD). Methods: We studied 207 consecutive patients (99 men, 108 women; age range, 17–84 years) who underwent intestinal biopsy for suspected CD. Patients presented with one or more of the following: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia,…

Androgen metabolism and biotransformation in nontumoral and malignant human liver tissues and cells

2009

There is indirect multiple evidence that hints at a potential role of sex steroids in development and progression of human hepatocellular carcinoma (HCC). In the present study, we have investigated androgen metabolism in a panel of human liver cancer cell lines (HA22T, Huh7, HepG2) and in normal, cirrhotic and malignant human liver tissues aiming to dissect the potential impact of individual enzyme activities and their products in normal and diseased human liver, both in vivo and in vitro. Using our intact cell analysis we were able to assess rates and pathways of androgen metabolism in living conditions. Overall, incubation of cultured cells or tissue minces with either testosterone (T) or…

Sex-Differences in the Pattern of Comorbidities, Functional Independence, and Mortality in Elderly Inpatients: Evidence from the RePoSI Register

2019

Background: The RePoSi study has provided data on comorbidities, polypharmacy, and sex dimorphism in hospitalised elderly patients. Methods: We retrospectively analysed data collected from the 2010, 2012, 2014, and 2016 data sets of the RePoSi register. The aim of this study was to explore the sex-differences and to validate the multivariate model in the entire dataset with an expanded follow-up at 1 year. Results: Among 4714 patients, 51% were women and 49% were men. The disease distribution showed that diabetes, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, and malignancy were more frequent in men but that hypertension, anaemia, osteoarthritis, de…

Natural approaches in metabolic syndrome management

2017

Metabolic syndrome (MetS) is characterized as a group of cardiometabolic risk factors that raise the risk for heart disease and other health problems, such as diabetes mellitus and stroke. Treatment strategies include pharmacologic interventions and supplementary (or "alternative") treatments. Nutraceuticals are derived from food sources (isolated nutrients, dietary supplements and herbal products) that are purported to provide health benefits, in addition to providing basic nutritional value. Nutraceuticals are claimed to prevent chronic diseases, improve health, delay the aging process, increase life expectancy, and support the structure and function of the body. The study of the benefici…

A key role for abdominal ultrasound examination in "difficult" diagnoses of celiac disease.

2010

Purpose To evaluate the usefulness of abdominal ultrasound examination (US) for the diagnostic workup of cases of suspected CD involving negative serum antibodies and difficult diagnosis. Materials and methods 524 consecutive patients with symptoms of suspected CD underwent an extensive diagnostic workup. 76 (14 %) were excluded since they were positive for serum anti-tTG and/or EmA antibodies. 377 were excluded since they were diagnosed with something other than CD or did not have the alleles encoding for HLA DQ 2 or DQ 8. A diagnosis of CD with negative serum antibodies was probable in 71 patients who underwent abdominal US and duodenal biopsy for histology evaluation. Results Intestinal …

Hepatitis C virus infection in hemodialyzed patients.

2007

In spite of our present improved knowledge of the epidemiology and pathways of contamination of the hepatitis C virus (HCV), infection still remains a public health problem. One category of patients who have suffered greatly from the consequences of HCV infection is certainly that of hemodialysis patients. In the past, in fact, their need for transfusions exposed these patients to infection and, as a result, subjects on dialysis for over 15 years are today paying the price for those inevitable transfusions, as the virus and its pathways of contagion were unknown then. However, still today, albeit at a much lower prevalence, even subjects with a shorter dialysis age present a higher prevalen…

Correlation between solubile adhesion molecules, TNF α malnutrition and inflammation in renal patients

2004

Two single nucleotide polymorphisms in the MICA gene and sMICA plasma levels are associated with hepatocellular carcinoma development in an Italian p…

2017

Background &amp; Aims: We investigated the relationships between MICA polymorphisms, sMICA levels and hepatocellular carcinoma (HCC) risk in HCC patients with chronic hepatitis C virus (HCV) infection. Methods.154 HCV-related HCC cases, 93 HCV-related liver cirrhosis (LC) cases and 244 healthy controls were genotyped using KASPTM SNP method. Levels of plasma soluble MICA (sMICA) were measured in 132 HCC, 90 LC patients and in 78 controls. Results. Genotyping of MICA rs2596542 showed that G/G genotype was significantly more frequent in HCC than in controls and in HCC than in LC patients. As for MICA rs2596538 allele C and C/C genotype were significantly more frequent in HCC than in controls …

Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy men-a randomized trial.

2013

Context and Objective Investigating the effects of lipid-lowering drugs on HDL subclasses has shown ambiguous results. This study assessed the effects of ezetimibe, simvastatin, and their combination on HDL subclass distribution. Design and Participants A single-center randomized parallel 3-group open-label study was performed in 72 healthy men free of cardiovascular disease with a baseline LDL-cholesterol of 111±30 mg/dl (2.9±0.8 mmol/l) and a baseline HDL-cholesterol of 64±15 mg/dl (1.7±0.4 mmol/l). They were treated with ezetimibe (10 mg/day, n = 24), simvastatin (40 mg/day, n = 24) or their combination (n = 24) for 14 days. Blood was drawn before and after the treatment period. HDL subc…

Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: How mutations can result in therapy resistance and how to overcome resistance

2012

// James A. McCubrey 1 , Linda S. Steelman 1 , William H. Chappell 1 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Giuseppe Montalto 2 , Melchiorre Cervello 3 , Massimo Libra 4 , Saverio Candido 4 , Grazia Malaponte 4 , Maria C. Mazzarino 4 , Paolo Fagone 4 , Ferdinando Nicoletti 4 , Jorg Basecke 5 , Sanja Mijatovic 6 , Danijela Maksimovic-Ivanic 6 , Michele Milella 7 , Agostino Tafuri 8 , Francesca Chiarini 9 , Camilla Evangelisti 9 , Lucio Cocco 10 , Alberto M. Martelli 9,10 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA 2 Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy 3 Consi…

Unexplained Elevated Serum Pancreatic Enzymes: A Reason to Suspect Celiac Disease

2006

BACKGROUND & AIMS: The frequency of elevated serum pancreatic enzymes in patients with celiac disease (CD) is unknown. The aim of this study was to evaluate the serum levels of pancreatic enzymes in CD patients. METHODS: Serum pancreatic isoamylase and lipase levels were assayed in 90 adult and 112 pediatric consecutive CD patients at diagnosis and after 12 months of gluten-free diet (GFD). Serum elastase and trypsin levels were assayed in a subgroup of adult CD patients. Pancreatic ultrasonography was also performed. RESULTS: Twenty-six adult (29%) and 29 pediatric (26%) CD patients exhibited elevated values of serum pancreatic amylase and/or lipase; trypsin was elevated in 69% and elastas…

The NF-kB inhibitors curcumin and DHMEQ exert antitumor synergy with cisplatin in hepatic cancer cells. Analysis of relationship to IL-6 production.

2006

Exocrine Pancreatic Function and Fat Malabsorption in Human Immunodeficiency Virus-Infected Patients

1999

BACKGROUND: Nutrients malabsorption frequently occurs in human immunodeficiency virus (HIV)-infected patients, but very few studies have investigated exocrine pancreatic digestive capacity in these patients. We therefore evaluated the frequency of exocrine pancreatic impairment and its eventual relation with fat malabsorption in HIV-infected patients. METHODS: Thirty-five HIV-infected patients (30 male, 5 female: mean age +/- standard deviation, 33.6 +/- 7.2 years) and 51 sex- and age-matched controls without gastroenterologic diseases were studied. In all subjects fecal elastase 1 (EL-1) was assayed, and fecal fat excretion was evaluated with the steatocrit test. RESULTS: Nineteen of 35 (5…

PPAR Agonists, Atherogenic Dyslipidemia and Cardiovascular Risk.

2016

Peroxisome proliferator-activated receptors (PPAR) are implicated in the pathology of several metabolic diseases including obesity, diabetes, and atherosclerosis. PPAR agonists exert multiple lipid modifying actions which are beneficial to the prevention of atherosclerosis. Such benefits in lipid lowering actions include improvements in atherogenic dyslipidemia that seems to be particularly expressed in individuals at higher cardiovascular (CV) risk. In addition, the favorable effects of PPAR agonists on different cardio-metabolic parameters are established in several metabolic conditions, such as diabetes mellitus, insulin resistance, and heightened systemic inflammation. The goal of this …

Early discontinuation of ribavirin in HCV-2 and HCV-3 patients responding to Peg-interferon alpha-2° and ribavirin

2009

SUMMARY. Guidelines for the treatment of patients infected with hepatitis C virus of genotypes 2 and 3 (HCV-2 and HCV-3, respectively) recommend a 24-week course of Peginterferon (Peg-IFN) alpha-2a combined with ribavirin, despite 50% of patients in registration trials attaining a sustained virologic response (SVR) following Peg-IFN alpha-2a monotherapy. The aim of this study was to delineate patient characteristics that might help to identify individuals likely to benefit from ribavirin discontinuation. One hundred and forty-four HCV-2- and HCV-3-infected patients initiated Peg-IFN alpha-2a (180 lg ⁄ week) and ribavirin (1000 or 1200 mg⁄ day); those with viral clearance at week 4 were rand…

Correlazione tra molecole di adesione, TNFalfa, malnutrizione ed infiammazione nei pazienti con insufficienza renale cronica, in emodialisi e con tra…

2004

Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

2013

Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in t…

Valore predittivo dei test sierologici nella diagnosi di malattia celiaca

2002

In the diagnostic work-up of celiac disease (CD) the simpler enzyme-linked immunosorbent assay (ELISA) for the identification of serum anti-transglutaminase (tTG) autoantibodies could substitute the immunofluorescence technique used for the detection of anti-endomysial antibodies (EmA). However, most of the studies on anti-tTG assay have considered pre-selected groups of patients and not consecutive subjects with suspected CD. The aim of this study was to compare the sensitivity, specificity and predictive value of anti-gliadin antibodies (AGA), EmA and two anti-tTG ELISAs, one based on guinea pig (gp)-tTG and the other on human (h)-tTG as antigens, in consecutive patients investigated for …

Potentiation of antitumor effects of NSAIDs by inhibition of MEK/ERK activity in human hepatocellular carcinoma cells

2005

Expression of HIP/PAP mRNA in Human Hepatoma Cell Lines

2002

The present study attempts to shed more light on the role of hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) in hepatoma cells. We initially examined, by reverse transcription-polymerase chain reaction (RT-PCR), the HIP/PAP transcripts present in human hepatoma cell lines of different origins and with different grades of differentiation and genetic profiles. We also used DNA sequencing analysis to investigate the structure of the HIP/PAP gene. Further investigation is necessary to define the role of HIP/PAP during the development of human hepatocellular carcinoma and to ascertain whether the use of different transcripts is helpful in regulating HIP/PAP expression …

PREVALENCE OF LIVER DISEASES IN A POPULATION OF IMMIGRANTS IN SICILY. ANALYSIS OF DAY-HOSPITAL ADMISSIONS IN A DEPARTMENT OF MIGRATION MEDICINE

2011

Pancreatic dysfunction and its association with fat malabsorption in HIV infected children

1998

Background—Nutrient malabsorption frequently occurs in HIV infected children, but very few studies have investigated exocrine pancreatic digestive capacity in these cases.Aims—To investigate pancreatic function in HIV infected children and to determine whether faecal fat loss, a prominent feature of intestinal dysfunction, is associated with pancreatic dysfunction.Patients—Forty seven children with HIV infection without apparent pancreatic disease and 45 sex and age matched healthy controls.Methods—Pancreatic function was evaluated by measuring elastase 1 concentration and chymotrypsin activity in stools by ELISA and colorimetric methods, respectively. Intestinal function was evaluated by m…