Dietary-suppression of hepatic lipogenic enzyme expression in intact male transgenic mice.

Aim: To study, in intact male transgenic mice, the effects of three diets based on olive oil and olive oil diet supplemented with lovastatin and orlistat on hepatic lipogenic enzymes expression, considered markers of cell proliferation.

Methods: Forty Apc(Min/+) mice were randomly divided into 4 groups and fed for 10 wk: olive oil (OO) group, n = 10 animals received a diet with olive oil 12%; olive oil plus lovastatin (LOVA) group, n = 10 animals received the same diet with olive oil supplemented with lovastatin 5 mg/kg; olive oil plus orlistat (OR) group, n = 10 animals fed the diet with olive oil supplemented with orlistat 50 mg/kg and SD group, n = 10 animals fed a standard diet. The activity of lipogenic enzymes and their gene expression were evaluated by radiometric and real-time reverse transcription-polymerase chain reaction assay, respectively.

Adipokine profile in celiac patients: differences in comparison with patients suffering from diarrhea-predominant IBS and healthy subjects.

OBJECTIVE. The role of adipokines such as resistin, leptin, and adiponectin could be pivotal in the molecular crosstalk between the inflamed intestine and the surrounding mesenteric adipose tissue. Our aims were to a) evaluate their circulating concentrations in patients with active celiac disease (ACD) and compare them to those in patients with diarrhea-predominant irritable bowel syndrome (IBS-d) and healthy subjects; b) establish the impact of genetic variability in resistin; and c) evaluate whether a 1-year gluten-free diet (GFD) modifies circulating concentrations of resistin, leptin, and adiponectin in celiac patients.

Antitumorigenic effect of dietary natural compounds via lipid metabolism modulation in Apc(Min/+) mice.

Aim: The aim of the present study was to evaluate the effects of a diet supplementation with either olive oil, or n-3 or n-6-polyunsaturatedFatty acids (PUFAs) on tumour development and gene expression for lipogenic enzymes in Apc(Min/+) mice.

Materials And Methods: In the control group, the mice received a standard diet, the OO group was fed on a diet with 12% olive oil, the OM-3 group with 12% salmon fish rich in n-3 PUFAs, the OM-6 group with 12% oenothera oil rich in n-6 PUFAs. Gene expression of lipogenic enzymes was evaluated by real-time reverse transcription polymerase chain reaction.

Hepatocellular carcinoma size: platelets, γ-glutamyl transpeptidase, and alkaline phosphatase.

Background: Thrombocytopenia is a cirrhosis surrogate which is associated with hepatocellular carcinoma (HCC) development.

Aims: To compare the clinical characteristics of HCC in the presence and absence of thrombocytopenia.

Methods: The baseline clinical data of a large cohort of randomly presenting, biopsy-proven HCC patients was examined for phenotypic patterns, after organizing the data by tumor size and subdivision into tumor size terciles.

Features of massive hepatocellular carcinomas.

Background: Massive hepatocellular carcinomas (HCCs) are uncommon and poorly characterized.

Aim: To characterize a large cohort of HCC patients with massive tumors, with documented baseline characteristics and survival data.

Methods: Records were examined of a cohort of 344 biopsy-proven and randomly presenting unresectable HCC patients with tumors of at least 10 cm diameter (massive), which were analyzed for their clinical characteristics and survival.

The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study.

Background: Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating levels of zonulin, glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF) and ghrelin and their relationship with intestinal permeability and chemotherapy induced diarrhea (CTD).

Methods: Sixty breast cancer patients undergoing an FEC60 regimen were enrolled, 37 patients completed the study.

Thrombocytosis and hepatocellular carcinoma.

Background: Thrombocytopenia has been reported to be both a risk factor for hepatocellular carcinoma (HCC) development as well as a prognostic factor. Many HCCs also occur in presence of normal platelets.

Aim: To examine a cohort of HCC patients with associated thrombocytosis.

Inulin-enriched pasta improves intestinal permeability and modifies the circulating levels of zonulin and glucagon-like peptide 2 in healthy young volunteers.

Apart from the intestinal environment, inulin induces physiological effects, which includes a reduction in glucose and lipid concentrations and modulation of gastrointestinal motility through the release of different peptides. We hypothesized that inulin-enriched pasta may also improve small intestine permeability in relation to zonulin and glucagon-like peptide 2 (GLP-2) levels in healthy young subjects. Twenty healthy, young male volunteers completed a randomized, double-blind crossover study consisting of a 2-week run-in period and two 5-week study periods (11% inulin-enriched or control pasta), with an 8-week washout period in between.

Antiproliferative, antioxidant and anti-inflammatory effects of hydroxytyrosol on human hepatoma HepG2 and Hep3B cell lines.

Background: Olive oil intake has been shown to induce beneficial effect on health. This study aimed to investigate the effects of olive oil polyphenol hydroxytyrosol (HT) on cell proliferation and its antioxidant and anti-inflammatory capacity in human hepatoma Hep3B and HepG2 cell lines.

Materials And Methods: Cell growth after HT treatment was measured by 3-(4,5 di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test.

Cannabinoid type 1 receptor gene polymorphism and macronutrient intake.

Background: Cannabinoid type 1 receptor (CB1-R) is a key mediator in the control of food intake and is linked to obesity.

Aim: To evaluate the relationship between CB1-R gene polymorphism and dietary macronutrient intake in elderly subjects.

Methods: This study included 118 subjects (60 males, 58 females) from a population survey carried out in southern Italy in 1992-1993 who were older than 65 years and previously characterized for CB1-R polymorphism (75 with GG wild-type genotype, 41 with heterozygous polymorphic allele AG, and 2 with genotype AA).

Intestinal microbiota, probiotics and human gastrointestinal cancers.

Introduction: Cancers of the gastrointestinal tract account for 25 % of all cancers and for 9 % of all causes of cancer death in the world, so gastrointestinal cancers represent a major health problem. In the past decades, an emerging role has been attributed to the interactions between the gastrointestinal content and the onset of neoplasia.

Methods: Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk.

Effects of low concentrations of regorafenib and sorafenib on human HCC cell AFP, migration, invasion, and growth in vitro.

Sorafenib was shown in clinical trial to enhance survival in hepatocellular carcinoma (HCC) patients, but with minimal tumor shrinkage. To correlate several indices of HCC growth at various drug concentrations, HCC cells were grown in various low concentrations of two multikinase inhibitors, regorafenib (Stivarga) and sorafenib (Nexavar) and their effects were examined on alpha-fetoprotein (AFP), cell growth, migration, and invasion. In two AFP positive human HCC cell lines, AFP was inhibited at 0.

Increased serum levels of lipogenic enzymes in patients with severe liver steatosis.

Background: Lipid metabolism is altered in subjects with liver steatosis. FAS is a key enzyme in de novo lipogenesis and both FAS gene expression and enzymatic activity are primarily regulated by metabolic signals in the liver. Lipoprotein lipase (LPL), the rate-limiting enzyme for the hydrolysis of core triglycerides, plays a pivotal role in lipid metabolism.

Antiproliferative and proapoptotic effects of viable or heat-killed Lactobacillus paracasei IMPC2.1 and Lactobacillus rhamnosus GG in HGC-27 gastric and DLD-1 colon cell lines.

Data from literature suggest the possible use of probiotics as chemopreventive agents against colon cancer, but few investigations are available on their effects on gastric cancer proliferation. In our previous study, a specific Lactobacillus, strain L. paracasei IMPC2.

Thrombocytopenia in relation to tumor size in patients with hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) size at diagnosis is important in management. Without screening programs, tumor size at diagnosis is heterogeneous.

Aims: To examine the clinical parameters related to tumor size.

Small hepatocellular carcinomas and thrombocytopenia.

Background: Clinical phenotypes of small and large hepatocellular carcinomas (HCCs) are not well characterized.

Aim: To evaluate the characteristics of small HCCs diagnosed by screening.

Method: A cohort of 430 small HCCs that were diagnosed through screening, were dichotomized according to a size of ≤ 3 cm or >3 cm maximum tumor diameter and compared for radiological and blood-test parameters.

Some new approaches to the management of hepatocellular carcinoma.

A concordance of multiple advances is changing the management of hepatocellular carcinoma (HCC). These include: (1) identification of preventable and treatable causal factors, including hepatitis B and obesity (non-alcoholic steatotic hepatitis [NASH]); (2) description of molecular and proteomic profiles for HCC prognosis, disease subtyping, and drug selection; (3) identification of circulating tumor cells for non-invasive molecular typing; (4) identification of tumor stem cells, for HCC subtyping and as treatment targets; (5) large numbers of multi-kinase inhibitors that are currently undergoing clinical trial assessment and comparison; (6) an array of newer therapies of different drug classes, aimed at a wide range of targets in cell growth, apoptosis, autophagy, and tumor invasion pathways; (7) newer regional chemotherapy and radiotherapy regimens and delivery systems; (8) the extension of liver transplantation to larger HCCs and its wider availability through use of living-related organ donors; (9) new radiological techniques to assess the changes in HCC vascularity associated with angiogenic drug actions; (10) re-evaluation of the importance of tumor biopsy to obtain molecular signatures; (11) recognition of the importance of non-tumor liver parenchyma for tumor growth control and as a source of prognostic profiling in HCC patients; (12) the evaluation of kinase- and other inhibitors in neo-adjuvant and adjuvant therapy associated with resection and liver transplant and minimization of transplant waiting list drop-out; (13) re-evaluation of the role or limitation of tumor responses, since kinase inhibitors can enhance survival without HCC size responses; and (14) the development of combination therapies to enhance tumor control rates, either using drugs targeting differing pathways, or kinase-inhibitors combined with either chemotherapy drugs or yttrium 90.

Fluoro-Sorafenib (Regorafenib) effects on hepatoma cells: growth inhibition, quiescence, and recovery.

To evaluate the growth-inhibitory properties of the potent multi-kinase antagonist Regorafenib (Fluoro-Sorafenib), which was synthesized as a more potent Sorafenib, a Raf inhibitor and to determine whether similar mechanisms were involved, human hepatoma cell lines were grown in the presence or absence of Regorafanib and examined for growth inhibition. Western blots were performed for Raf targets, apoptosis, and autophagy. Regorafenib inhibited growth of human Hep3B, PLC/PRF/5, and HepG2 cells in a concentration- and time-dependent manner.

A significant role of lipogenic enzymes in colorectal cancer.

In this review, we summarize recent progress regarding the study of the main enzymes of lipid metabolism involved in colorectal cancer development, namely of a) farnesyltransferase (Ftase), a cytosolic enzyme that catalyzes the first step in the protein farnesylation; b) farnesyl diphosphate synthase (FPPS, which yields FPP, a substrate for Ftase; c) fatty acid synthase (FAS), an enzyme required for the conversion of acetyl-CoA and malonyl-CoA to palmitate; and d) lipoprotein lipase (LPL), the crucial enzyme for intravascular catabolism of triglyceride-rich lipoproteins. Alterations in the levels of these enzymes may contribute to a cell growth advantage acquired during the carcinogenic process and to the development of malignancy. We have demonstrated an elevated Ftase activity in human colorectal cancer (CRC), with differences in Ftase activity related to histological grading, tumor location and KRAS mutation status.

Low levels of lipogenic enzymes in peritumoral adipose tissue of colorectal cancer patients.

Lipoprotein lipase (LPL) is the crucial enzyme for intravascular catabolism of triglyceride-rich lipoproteins. Fatty acid synthase (FAS) is a key anabolic enzyme that catalyzes the terminal steps in the novo biosynthesis of 18:2n-6. The involvement of both LPL and FAS in tumor biology has been widely demonstrated in different studies and to verify whether there are regional differences in the expression of these enzymes in visceral adipose tissue from patients with colorectal cancer might be representative of events which sustain tumor growth.

Increased soluble leptin receptor levels are associated with advanced tumor stage in colorectal cancer patients.

Background: The leptin receptor is involved in modulating leptin activity, acting as a carrier protein. A link between leptin or leptin receptor and cancer development has been proposed and here, the hypothesis that leptin and its receptor might be implicated in colorectal cancer (CRC) progression and invasion was investigated.

Patients And Methods: A total of 71 consecutive patients with CRC were enrolled in the study.

Serum levels of fatty acid synthase in colorectal cancer patients are associated with tumor stage.

Purpose: Fatty acid synthase is a common phenotype to various human cancers including those of prostate, colon, lung, endometrium, and stomach. Increased fatty acid synthase levels have been detected in serum from patients with breast and pancreatic cancer. In this study, serum levels of fatty acid synthase were measured in colorectal cancer patients at different stages of disease.

Involvement of estrogen receptor-related receptors in human ovarian endometriosis.

Objective: To determine whether decreased estrogen receptor alpha (ER-α) expression in endometriotic lesions could be balanced by an increased expression of estrogen receptor-related receptors (ERRs). To evaluate whether ERR-α expression is influenced by hormonal change in fertile and menopausal women.

Design: Prospective controlled study.