PTEN in liver diseases and cancer

The phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt axis is a key signal transduction node that regulates crucial cellular functions, including insulin and other growth factors signaling, lipid and glucose metabolism, as well as cell survival and apoptosis. In this pathway, PTEN acts as a phosphoinositide phosphatase, which terminates PI3Kpropagated signaling by dephosphorylating PtdIns(3,4)P2 and PtdIns(3,4,5)P3. However, the role of PTEN does not appear to be restricted only to PI3K signaling antagonism, and new functions have been recently discovered for this protein. In addition to the well-established role of PTEN as a tumor suppressor, increasing evidence now suggests that a dysregulated PTEN expression and/or activity is also linked to the development of several hepatic pathologies. Dysregulated PTEN expression/activity is observed with obesity, insulin resistance, diabetes, hepatitis B virus/hepatitis C virus infections, and abusive alcohol consumption, whereas mutations/deletions have also been associated with the occurrence of hepatocellular carcinoma. Thus, it appears that alterations of PTEN expression and activity in hepatocytes are common and recurrent molecular events associated with liver disorders of various etiologies. These recent f indings suggest that PTEN might represent a potential common therapeutic target for a number of liver pathologies.

phosphatase and tensin homolog is a differential diagnostic marker between nonalcoholic and alcoholic fatty liver disease

AIM: To investigate the protein expression of phosphatase and tensin homolog(PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease.METHODS: PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffinembedded liver sections of patients with non-alcoholic fatty liver disease(NAFLD)(n = 44) or alcoholic liver disease(ALD)(n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients' clinical history.RESULTS: In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis(r = 0.3061, P = 0.0459) and the BMI(r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor(P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients(P < 0.0001).CONCLUSION: PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN immunohistochemical detection could help in the differential diagnosis of NAFLD and ALD.

Computer Science Tools for Manual Editing of Computed Tomographic Images: Impact on the Quality of 3D Printed Models

Background: Three-dimensional printing (3DP) technologies are a trendsetting topic, also in the field of surgery. Preoperative planning for maxillofacial and neurological surgery, for instance, increasingly involves skull models obtained by 3DP. However, the cranial replicas currently used in this context have been shown to not reproduce the exact anatomy of the individual patient undergoing surgery. Objective: The present study aimed at investigating the extent to which manual editing, using current computer software tools, can improve skull models derived from medical images. Methods: Skull computed tomography (CT) was obtained on three cadavers and?sent to three institutions that provide preoperative 3DP services. Each institute independently?performed 3D reconstructions, including routine manual editing, and subsequently produced the replicas. The models were then qualitatively compared with the respective original skull. For?quantitative comparison surface scans of particular regions of interest were made and the deviations assessed using 3-matic software (Materialise, Leuven, Belgium). Results: Routine manual editing of CT images resulted in replicas that were clear improvements over automatically generated reconstructions. This was particularly the case for teeth artefacts and thin-walled entities (e.g. paranasal sinuses). Conversely, however, many anatomical structures remained incorrectly rendered (e.g. orbitae, pterygoid processes, and sella turcica). Extraosseous calcifications had regularly not been removed. After extensive manual editing, however, replicas were able to provide largely submillimeter accuracy (mean deviation 0.2496 mm;standard deviation ±0.2276 mm). Conclusions: This study confirms that manual editing with current computer science tools does improve the quality of CT-based 3D printed skull models. But, it also demonstrates that a number of structures remain largely incorrectly rendered when edited in the presently used surgical framework. Conversely, it shows that highly accurate replicas are feasible, provided that extensive manual editing is performed.