PI3K Functions in Cancer Progression, Anticancer Immunity and Immune Evasion by Tumors

The immunological surveillance of tumors relies on a specific recognition of cancer cells and their associate antigens by leucocytes of innate and adaptive immune responses. However, a dysregulated cytokine release can lead to, or be associated with, a failure in cell-cell recognition, thus, allowing cancer cells to evade the killing system. The phosphatidylinositol 3-kinase (PI3K) pathway regulates multiple cellular processes which underlie immune responses against pathogens or malignant cells. Conversely, there is accumulating evidence that the PI3K pathway is involved in the development of several malignant traits of cancer cells as well as their escape from immunity. Herein, we review the counteracting roles of PI3K not only in antitumor immune response but also in the mechanisms that cancer cells use to avoid leukocyte attack. In addition, we discuss, from antitumor immunological point of view, the potential benefits and disadvantages arising from use of anticancer pharmacological agents targeting the PI3K pathway

Tissue expression of Squamous Cellular Carcinoma Antigen (SCCA) is inversely correlated to tumor size in HCC

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate squamous cellular carcinoma antigen (SCCA) in serum and in tumoral and paired peritumoral tissues. We studied 27 patients with liver cirrhosis (LC) and 55 with HCC: 20 with a single nodule < 3 cm (s-HCC) and 35 with a single nodule > 3 cm or multifocal (l-HCC).</p> <p>Methods</p> <p>Serum SCCA was measured by the ELISA kit, and in frozen tissues by immunohistochemistry, quantified with appropriate imaging analysis software and expressed in square microns. Continuous variables are reported as means and 95% confidence intervals. Comparisons between independent groups were performed with a generalized linear model and Tukey grouping. Pearson's correlation coefficients were determined to evaluate relations between markers. Qualitative variables were summarized as count and percentage. Statistical significance was set at p-value < 0.05.</p> <p>Results</p> <p>Serum SCCA values in LC patients were 0.41 (0.31–0.55) ng/ml and statistically different from both HCC groups: 1.6 (1.0–2.6) ng/ml in s-HCC, 2.2 (1.28–2.74) ng/ml in l-HCC. SCCA in hepatic tissue was 263.8 (176.6–394.01) μm²in LC patients, statistically different from values in s-HCC: 1163.2 (863.6–1566.8) μm²and l-HCC: 625.8 (534.5–732.6). All pairwise comparisons between groups yielded statistically significant differences. Tumoral SCCA resulted linearly related with nodule size, showing a statistically significant inverse relation between the two variables (b = -0.099, p = 0.024).</p> <p>Conclusion</p> <p>There was no statistically significant correlation between tissue and serum levels of SCCA. The significantly stronger expression of SCCA in smaller compared to larger HCC could be important for early HCC detection. However, the increased expression in peritumoral tissue could affect the significance of serological detection.</p

Immunological responses in patients with tuberculosis and in vivo effects of acetyl-L-carnitine oral administration

Tuberculosis (TBC) is characterized by a complex immune response which parallels the clinical course of the disease. In this respect, acquired resistance, delayed hypersensitivity reaction and anergy are the main types of immune reactivity to mycobacterial antigens. In view of the presence of nonspecific and specific immune deficits in TBC patients, a clinical trial was carried out in a group of 20 individuals with active pulmonary TBC by oral administration of acetyl-L-carnitine (ALC). This drug, which has been shown to possess immunomodulating activities, was able to upregulate the T-dependent antibacterial activity in TBC patients after 30 days' treatment, while the same activity decreased in patients receiving placebo only. On the other hand, ALC did not modify serum levels of tumour necrosis factor-α, in the same individuals. This cytokine plays a detrimental rather than beneficial role in TBC pathogenesis. In the light of these data, ALC seems to be a powerful immunomodulator in the course of Mycobacterium tuberculosis infection and other mycobacteriosis

Setup of Extruded Cementitious Hollow Tubes as Containing/Releasing Devices in Self-Healing Systems

N.M.P. is supported by the European Research Council (ERC Starting Grant Ideas 2011 BIHSNAM No. 279985 on ‘Bio-inspired hierarchical supernanomaterials’, ERC Proof of Concept (PoC) 2013-1 REPLICA2 No. 619448 on ‘Large-area replication of biological anti-adhesive nanosurfaces’, ERC PoC 2013-2 KNOTOUGH no. 632277 on ‘Super-tough knotted fibres’), by the European Commission under the Graphene Flagship (WP10 ‘Nanocomposites’, No. 604391) and by the Provincia Autonoma di Trento (‘Graphene nanocomposites’, No. S116/2012-242637 and regional deliberation No. 2266)

HCC Heterogeneity: Molecular Pathogenesis and Clinical Implications

Background: Hepatocellular carcinoma (HCC) poses a major challenge because of the extreme variability of the clinical outcome, which makes it difficult to properly stage the disease and thereby estimate the prognosis. There is growing evidence that this heterogeneous clinical behavior is attributable to several different biological pathways. A novel approach to mapping these differences is by investigating the epigenetics associated with certain clinical aspects