Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma.

BACKGROUND: Chronic inflammation is involved in the initiation and progression of various cancers, including liver cancer. The current study focuses on the characterization of the peripheral immune response in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients, before and after surgical procedure, in order to assess the effect of tumor resection in the immune system homeostasis and to determine possible prognostic factors associated with high-grade tumors. We developed a whole-blood assay to monitor immune alterations and functional competence of peripheral monocytes in a group of 10 healthy individuals (HG), in 20 HCC patients and 8 CCA patients, by multi-color flow cytometry, qRT-PCR, and ELISA techniques. RESULTS: The qRT-PCR analysis showed an upregulation of TNFα expression by classical and intermediate monocytes purified from HCC patients presenting tumors in grade G3-G4 as compared to G1-G2 HCC patients. Moreover, ELISA assay confirmed elevated serum levels of TNFα in G3-G4 compared to G1-G2 HCC patients. A significant decrease of circulating non-classical monocytes was detected in both CCA and HCC patients before and after surgical procedure. In addition, a functional defect in circulating classical and intermediate monocytes was observed in both groups of cancer patients when compared to the HG, with partial recovery after the surgical intervention. CONCLUSIONS: This integrated analysis permitted the identification of altered functional competence of monocyte subsets in CCA and HCC patients. In addition, our results point to a potential role of TNFα as a prognostic peripheral biomarker in HCC patients, indicating the presence of high-grade tumors that should be further validated.

Functional and Phenotypic Characterization of Tumor-Infiltrating Leukocyte Subsets and Their Contribution to the Pathogenesis of Hepatocellular Carcinoma and Cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response. In the present study, we evaluated the tumor-infiltrating leukocyte (TIL) populations in 21 HCC patients and 8 CCA patients by flow cytometry immediately after the surgical procedure. Moreover, CD4+ T cells, CD8+ T cells, monocytes, and macrophages were purified by cell sorting for further analysis of gene expression by quantitative reverse-transcription polymerase chain reaction. Regarding tumor-infiltrating macrophages, we observed a significantly higher expression of markers associated with M2 phenotype and a higher expression of PD-L1 in patients with HCC in comparison to CCA. In addition, for HCC patients, we found a significant increase in the expression of CD200R in macrophages from tumors that were in grade G3-G4 as compared to tumors in grade G1-G2. Besides, a significantly higher frequency of tumor-infiltrating lymphocytes, CD8+CD56+ T cells, and natural killer cells was detected in HCC biopsies in comparison to CCA. In summary, this study has revealed functional and phenotypic differences in TIL cell subpopulations between CCA and HCC, as well as among different histopathological grades and tumor aggressiveness degrees, and it has provided evidence to better understand the tumor immune microenvironment of CCA and HCC.

Lipoxidation and cancer immunity.

Lipoxidation is a well-known reaction between electrophilic carbonyl species, formed during oxidation of lipids, and specific proteins that, in most cases, causes an alteration in proteins function. This can occur under physiological conditions but, in many cases, it has been associated to pathological process, including cancer. Lipoxidation may have an effect in cancer development through their effects in tumour cells, as well as through the alteration of immune components and the consequent modulation of the immune response. The formation of protein adducts affects different proteins in cancer, triggering different mechanism, such as proliferation, cell differentiation and apoptosis, among others, altering cancer progression. The divergent results obtained documented that the formation of lipoxidation adducts can have either anti-carcinogenic or pro-carcinogenic effects, depending on the cell type affected and the specific adduct formed. Moreover, lipoxidation adducts may alter the immune response, consequently causing either positive or negative alterations in cancer progression. Therefore, in this review, we summarize the effects of lipoxidation adducts in cancer cells and immune components and their consequences in the evolution of different types of cancer.

Ofidismo en la península Ibérica / Snake venom poisoning in the Iberian peninsula

En la península Ibérica hay 13 especies autóctonas de ofidios. Diez de ellas pertenecen a la familia de los colúbridos, que no son venenosos excepto la culebra bastarda y la culebra de cogulla. Las 3 especies de vipéridos (víbora áspid, víbora hocicuda y víbora de Seoane) son venenosas y son la causa más frecuente de envenenamiento por ofidios en España. Una serie de rasgos permiten diferenciar ambas familias e incluso identificar a cada una de las especies. La identificación de la especie y de los signos y síntomas de envenenamiento son importantes para el correcto tratamiento del paciente. En esta actualización se exponen las claves que permiten diferenciar las diversas especies de ofidios, así como las bases de la terapéutica extrahospitalaria (primeros auxilios y tratamiento inicial en el centro de salud) y hospitalaria de las mordeduras de serpiente (AU)

Thirteen species of snakes are native to the Iberian peninsula. Ten belong to the Colubridae family and, except for the Montpellier snake and the False smooth snake, they are not poisonous. The three species of Viper (Asp viper, Snub-nosed viper and Seoane’s viper) are poisonous and are the most common cause of snake venom poisoning in Spain. A number of features differentiate the two families and even enable individual species to be identified. This identification of the species, as well as the signs and symptoms of poisoning are important for correct patient management. This update outlines the key features that enable the various species of snakes to be identified, and the basis of outpatient (first aid and initial medical treatment) and hospital treatment of snake bites (AU)