Tumor necrosis factor gene polymorphism in migraine

OBJECTIVE: To better define the involvement of human leukocyte antigen region (HLA) genes in migraine via an association study of the tumor necrosis factor (TNF) genes, located in the HLA class III region, with migraine with and without aura. BACKGROUND: Migraine without aura and migraine with aura are disorders involving multiple factors-environmental and genetic. In a previous study, we hypothesized a protective role for the HLA-DR2 antigen, providing additional basis for the proposed genetic heterogeneity between migraine without aura and migraine with aura. The cytokines produced by TNF genes are polypeptide effectors of inflammatory reaction and endothelial function. METHODS: Tumor necrosis factor (TNF)-308 (TNF-308A and TNF-308G alleles) and lymphotoxin alpha (TNFB*1 and TNFB*2 alleles) polymorphisms were analyzed by the NcoI-cleaved polymerase chain reaction-amplified fragments in 47 patients with migraine without aura, 32 patients with migraine with aura, and 101 migraine-free controls. RESULTS: The frequency of TNFB*2 allele was significantly increased in our patients with migraine without aura as compared with the control group (78.72% versus 61.4%, Pc =.004), but no significant differences were found between patients with migraine with aura and controls. Additionally, there was a significant decrease of TNFB*1 homozygotes in patients with migraine without aura compared with the control group (2.13% versus 16.8%, Pc =.0201). Carriage of the TNFB*2 allele confers a high risk for the development of migraine without aura. No significant association was found at TNF-308 polymorphism. CONCLUSION: These data support the hypothesis that lymphotoxin alpha could be a susceptibility gene in migraine without aura and confirm previous data indicating that migraine with and without aura are distinct entities with different genetic backgrounds

The Inflammatory Microenvironment in Hepatocellular Carcinoma: A Pivotal Role for Tumor-Associated Macrophages

Hepatocellular carcinoma (HCC) is one of the most common and aggressive human cancers worldwide. HCC is an example of inflammation-related cancer and represents a paradigm of the relation occurring between tumor microenvironment and tumor development. Tumor-associated macrophages (TAMs) are a major component of leukocyte infiltrate of tumors and play a pivotal role in tumor progression of inflammation-related cancer, including HCC. Several studies indicate that, in the tumor microenvironment, TAMs acquire an M2-polarized phenotype and promote angiogenesis, metastasis, and suppression of adaptive immunity through the expression of cytokines, chemokines, growth factors, and matrix metalloproteases. Indeed, an established M2 macrophage population has been associated with poor prognosis in HCC. The molecular links that connect cancer cells and TAMs are not completely known, but recent studies have demonstrated that NF-κB, STAT-3, and HIF-1 signaling pathways play key roles in this crosstalk. In this paper, we discuss the current knowledge about the role of TAMs in HCC development, highlighting the role of TAM-derived cytokines, chemokines, and growth factors in the initiation and progression of liver cancer and outlining the signaling pathways involved in the interplay between cancer cells and TAMs

MicroRNAs in the DNA Damage/Repair Network and Cancer

Cancer is a multistep process characterized by various and different genetic lesions which cause the transformation of normal cells into tumor cells. To preserve the genomic integrity, eukaryotic cells need a complex DNA damage/repair response network of signaling pathways, involving many proteins, able to induce cell cycle arrest, apoptosis, or DNA repair. Chemotherapy and/or radiation therapy are the most commonly used therapeutic approaches to manage cancer and act mainly through the induction of DNA damage. Impairment in the DNA repair proteins, which physiologically protect cells from persistent DNA injury, can affect the efficacy of cancer therapies. Recently, increasing evidence has suggested that microRNAs take actively part in the regulation of the DNA damage/repair network. MicroRNAs are endogenous short noncoding molecules able to regulate gene expression at the post-transcriptional level. Due to their activity, microRNAs play a role in many fundamental physiological and pathological processes. In this review we report and discuss the role of microRNAs in the DNA damage/repair and cancer

Additional file 2: Figure S2. of MicroRNA expression analysis in high fat diet-induced NAFLD-NASH-HCC progression: study on C57BL/6J mice

MiRNAs differentially modulated during the progression of the hepatic damage. (A) RQ (relative quantification) values ± SE (Y axis) obtained by comparing HF to LF pooled RNAs from hepatic tissues. (B) RQ values ± SE (Y axis) of pooled RNAs from tumor tissues with respect to pooled RNAs from HF hepatic non-tumor tissues. Results are from 3 replicates. Global normalization mode was used for the analysis. Samples marked with the asterisk show P ≤ 0.05. (PDF 284 kb

Additional file 1: Figure S1. of MicroRNA expression analysis in high fat diet-induced NAFLD-NASH-HCC progression: study on C57BL/6J mice

Inflammatory infiltrate. Lymphocytes (green arrows), plasma cells (yellow arrows), macrophages (red arrows), and PMN (blue arrow). (PPTX 1448 kb