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

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

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

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

The Effect of Three Mediterranean Diets on Remnant Cholesterol and Non-Alcoholic Fatty Liver Disease: A Secondary Analysis.

BACKGROUND: Elevated fasting remnant cholesterol (REM-C) levels have been associated with an increased cardiovascular risk in patients with metabolic syndrome (Mets) and Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to estimate the effect of different diets on REM-C levels in patients with MetS, as well as the association between NAFLD and REM-C. METHODS: This is a secondary analysis of the MEDIDIET study, a parallel-arm Randomized Clinical Trial (RCT). We examined 237 people with MetS who underwent Liver Ultrasound (LUS) to assess the NAFLD score at baseline, 3-, and 6-months follow-up. Subjects were randomly assigned to the Mediterranean diet (MD), Low Glycemic Index diet (LGID), or Low Glycemic Index Mediterranean diet (LGIMD). REM-C was calculated as [total cholesterol-low density lipoprotein cholesterol (LDL-C)-high density lipoprotein cholesterol (HDL-C)]. RESULTS: REM-C levels were higher in subjects with moderate or severe NAFLD than in mild or absent ones. All diets had a direct effect in lowering the levels of REM-C after 3 and 6 months of intervention. In adherents subjects, this effect was stronger among LGIMD as compared to the control group. There was also a significant increase in REM-C levels among Severe NAFLD subjects at 3 months and a decrease at 6 months. CONCLUSIONS: fasting REM-C level is independently associated with the grade of severity of NAFLD. LGIMD adherence directly reduced the fasting REM-C in patients with MetS.

Women in LOVe: Lacto-Ovo-Vegetarian Diet Rich in Omega-3 Improves Vasomotor Symptoms in Postmenopausal Women. An Exploratory Randomized Controlled Trial.

OBJECTIVES: In the postmenopausal period, most women suffer vasomotor symptoms (VMS). It is well-known that VMS can worsen the quality of life. Diet seems to play a relevant role in the development of VMS, but the effect of diet on VMS is mainly limited to observational studies, and analyses of nutritional supplements. The aim of this study was thus to determine the efficacy of a lactoovo- vegetarian (LOVe) diet rich in omega-3 fatty acids vs. a lacto-ovo-vegetarian diet rich in EVO (extra-virgin olive oil) in reducing VMS frequency in postmenopausal women. METHODS: A two-arms (lacto-ovo-vegetarian diet with EVO vs. lacto-ovo-vegetarian diet rich in omega-3) randomized-controlled trial with a follow-up period of 16 weeks. We considered as primary outcome the change in the Kupperman index (follow-up vs. baseline evaluation, reported as delta, D) and in its subscales. Secondary outcomes included changes in common anthropometric and biohumoral measurements. RESULTS: Among 54 women randomly assigned to a study group, 40 (mean age 55.1±5.4 years) completed the study and complied with their assigned diet. Women randomized to the omega-3 group (n=18) showed significant improvements, compared to the EVO group (n=22), in Kupperman index (Δ=-11.4±9.8 vs. -5.9±8.2; p=0.045), hot flashes (Δ=-3.3±3.4 vs. -1.3±2.6; p=0.04), and a marginally significant improvement in nervousness (Δ=-1.7±1.7 vs. -0.8±1.5; p=0.07). No significant differences were observed for the secondary outcomes. No relevant side effects were reported. CONCLUSION: After 16 weeks, a lacto-ovo-vegetarian diet rich in omega-3 reduced VMS frequency in postmenopausal women more than the lacto-ovo-vegetarian diet rich in EVO.

Serum 90K/Mac-2 binding protein (Mac-2BP) as a response predictor to peginterferon and ribavirin combined treatment in HCV chronic patients.

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

Detection of 90K/MAC-2BP in the seminal plasma of infertile males with accessory gland infection and the autoimmune pathogenetic hypothesis.

The purpose of the study was to evaluate 90K/MAC-2BP, a glycoprotein member of the Scavenger Receptor Cystein Rich superfamily, in the seminal plasma of infertile male patients with male accessory gland infection in order to investigate a putative autoimmune pathogenesis. 90K seminal concentration and sperm parameters were evaluated in 50 patients with male accessory gland infection at baseline and after cycles of treatment with Levofluoxacin 500 mg daily for 15 days plus serratiopeptidase 10 mg daily for 30 days. Treatment was continued for up to 6 cycles in cases of persistant bacteriospermia and/or clinical and ejaculatory signs of the disease. Patients with persistant male accessory gland infection after 6 cycles were defined as nonresponders. The same parameters were evaluated at baseline and after a 2-month period in 30 healthy controls. Patients with male accessory gland infection showed impaired sperm parameters and had lower seminal 90K concentration compared to controls. After treatment, seminal 90K level significantly increased in patients compared to controls. Twenty-two patients responded to treatment (44%), while 28 were nonresponders (56%). No difference in pretreatment and posttreatment sperm parameters and seminal 90K was observed between the 2 subgroups. Thirteen patients (26%) had identifiable bacteriospermia: significantly less pretreatment seminal 90K was observed compared to patients without bacteriospermia. Seminal 90K is decreased in patients with male accessory gland infection, and may be restored by a treatment with quinolones. However, the clinical utility of a 90K assay in these patients remains uncertain, as its level is not predictive of response to treatment.