Deleted in Liver Cancer 2 (DLC2) protein expression in hepatocellular carcinoma

Deleted in Liver Cancer (DLC) proteins belong to the family of RhoGAPs and are believed to operate as negative regulators of the Rho family of small GTPases. So far, the role of the first identified member from the DLC family, DLC1, was established as a tumor suppressor in hepatocellular carcinoma. The function of its close family relative, DLC2 is unequivocal. In the present study we attempted to determine whether the loss of DLC2 is a common feature of hepatocellular carcinoma tissue. We examined two types of hepatocellular carcinoma- typical and fibrolamellar one. Our analysis revealed that DLC2 protein is not diminished in cancer tissue when compared to non-cancerous liver specimens. What is more, we observed DLC2 to be more abundantly expressed in cancer tissue, particularly in tumors with the inflammation background. In addition, we found that DLC2 gene status was diploid in virtually all tumor samples examined. Our results indicate that DLC2 is not diminished in hepatocellular carcinoma cells. It appears that members of the DLC family, although structurally highly related, may function differently in cancer cells

Loss of the Orphan Nuclear Receptor SHP Is More Pronounced in Fibrolamellar Carcinoma than in Typical Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) remains a major problem in oncology. The molecular mechanisms which underlie its pathogenesis are poorly understood. Recently the Small Heterodimer Partner (SHP), an orphan nuclear receptor, was suggested to be involved as a tumor suppressor in hepatocellular carcinoma development. To date, there are no such studies regarding fibrolamellar carcinoma, a less common variant of HCC, which usually affects young people and displays distinct morphological features. The aim of our project was to evaluate the SHP levels in typical and fibrolamellar hepatocellular carcinoma with respect to the levels of one of the cell cycle regulators, cyclin D1. We assessed the immunoreactivity levels of SHP and cyclin D1 in 48 typical hepatocellular carcinomas, 9 tumors representing the fibrolamellar variant, 29 non malignant liver tissues and 7 macroregenerative nodules. We detected significantly lower SHP immunoreactivity in hepatocellular carcinoma when compared to non malignant liver tissue. Moreover, we found that SHP immunoreactivity is reduced in fibrolamellar carcinoma when compared to typical hepatocellular carcinoma. We also found that SHP is more commonly lost in HCC which arises in the liver with steatosis. The comparison between the cyclin D1 and SHP expression revealed the negative correlation between these proteins in the high grade HCC. Our results indicate that the impact of loss of SHP protein may be even more pronounced in fibrolamellar carcinoma than in a typical form of HCC. Further investigation of mechanisms through which the loss of SHP function may influence HCC formation may provide important information in order to design more effective HCC therapy

Changes in Sedentary and Active Lifestyle, Diet Quality and Body Composition Nine Months after an Education Program in Polish Students Aged 11–12 Years: Report from the ABC of Healthy Eating Study

The sustainability of education focused on improving the dietary and lifestyle behaviours of teenagers has not been extensively studied. The aim of this study was to determine the sustainability of diet-related and lifestyle-related school-based education on sedentary and active lifestyle, diet quality and body composition of Polish pre-teenagers in a medium-term follow-up study. An education-based intervention study was carried out on 464 students aged 11⁻12 years (educated/control group: 319/145). Anthropometric measurements were taken and body mass index (BMI) and waist-to-height ratios (WHtR) were calculated, both at the baseline and after nine months. Dietary data from a short-form food frequency questionnaire (SF-FFQ4PolishChildren) were collected. Two measures of lifestyle (screen time, physical activity) and two diet quality scores (pro-healthy, pHDI, and non-healthy, nHDI) were established. After nine months, in the educated group (vs. control) a significantly higher increase was found in nutrition knowledge score (mean difference of the change: 1.8 points) with a significantly higher decrease in physical activity (mean difference of the change: −0.20 points), nHDI (−2.3% points), the z-WHtR (−0.18 SD), and the z-waist circumference (−0.13 SD). Logistic regression modelling with an adjustment for confounders revealed that after nine months in the educated group (referent: control), the chance of adherence to a nutrition knowledge score of at least the median was over 2 times higher, and that of the nHDI category of at least the median was significantly lower (by 35%). In conclusion, diet-related and lifestyle-related school-based education from an almost one-year perspective can reduce central adiposity in pre-teenagers, despite a decrease in physical activity and the tendency to increase screen time. Central adiposity reduction can be attributed to the improvement of nutrition knowledge in pre-teenagers subjected to the provided education and to stopping the increase in unhealthy dietary habits

The cyclin D1 expression in hepatocellular carcinoma.

<p>A- the immunoreactivity of cyclin D1 in HCC tumor; B- the cyclin D1 immunoreactivity in fibrolamellar carcinoma; scale bar 5 µm; C- Spearman's rank graph showing a negative correlation between the SHP and cyclin D1 immunoreactivity in G3 hepatocellular carcinoma.</p

SHP immunoreactivity in normal liver.

<p>A, B – immunohistochemical staining of the normal hepatic lobule; C, D- immunofluorescence staining showing exclusively nuclear (C) or cytoplasmic (D) SHP localization in different lobules; scale bar: A 100 µm; B 20 µm; C,D 25 µm. E- result of the SHP immunohistochemistry preceded with (lower image) or without (upper image) anti-SHP blocking antibody; F- Western blot analysis of three liver (LV1–LV3) lysates, the SHP protein present in a single band; G- Result of the RT-PCR study showing the SHP mRNA in the normal liver; GAPDH mRNA was used as a control.</p

Clinicopathological characteristic of patients with results of the immunostaining.

<p>Abbreviations: Ca cm maximal tumor size in cm; Inflamm inflammation; G tumor grade; S stage; N normal; C cirrhosis; R HCC recurrence;</p><p>*data not available; n/a not applicable.</p

SHP immunoreactivity in macroregenerative nodules.

<p>Note uniform staining of all hepatocytes; scale bar A-100 µm, B-50 µm.</p

Tyk2 and stat3 regulate brown adipose tissue differentiation and obesity

Mice lacking the Jak tyrosine kinase member Tyk2 become progressively obese due to aberrant development of Myf5+ brown adipose tissue (BAT). Tyk2 RNA levels in BAT and skeletal muscle, which shares a common progenitor with BAT, are dramatically decreased in mice placed on a high-fat diet and in obese humans. Expression of Tyk2 or the constitutively active form of the transcription factor Stat3 (CAStat3) restores differentiation in Tyk2−/− brown preadipocytes. Furthermore, Tyk2−/− mice expressing CAStat3 transgene in BAT also show improved BAT development, normal levels of insulin, and significantly lower body weights. Stat3 binds to PRDM16, a master regulator of BAT differentiation, and enhances the stability of PRDM16 protein. These results define Tyk2 and Stat3 as critical determinants of brown fat lineage and suggest that altered levels of Tyk2 are associated with obesity in both rodents and humans