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The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p = 0.002) and in males (p = 0.003), but not in females separately (p = 0.3). This association was found in tobacco smokers (p = 0.003) and in BE patients without reflux (p = 0.004), but not in nonsmokers (p = 0.2) or those with reflux (p = 0.036). SNPs within JMJD1C were associated with risk of EAC in females (p = 0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed. [ABSTRACT FROM AUTHOR]

• Introduction • Selectins • Selectin ligands - Sialyl Lewis antigens - CD44 (H-CAM) • Conclusions – future perspectives The colonization of the liver by colorectal cancer (CRC) cells is a complicated process which includes many stages, until macrometastases occur. The entrapment of malignant cells within the hepatic sinusoids and their interactions with resident non-parenchymal cells are considered very important for the whole metastatic sequence. In the sinusoids, cell connection and signalling is mediated by multiple cell adhesion molecules, such as the selectins. The three members of the selectin family, E-, P- and L-selectin, in conjunction with sialylated Lewis ligands and CD44 variants, regulate colorectal cell communication and adhesion with platelets, leucocytes, sinusoidal endothelial cells and stellate cells. Their role in CRC liver metastases has been investigated in animal models and human tissue, in vivo and in vitro, in static and shear flow conditions, and their key-function in several molecular pathways has been displayed. Therefore, trials have already commenced aiming to exploit selectins and their ligands in the treatment of benign and malignant diseases. Multiple pharmacological agents have been developed that are being tested for potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the commonest malignancies in the “developed” world. The liver constitutes the main host organ for its distant metastases which, when present, augur a bad prognosis for the disease. Kupffer cells (KCs) are macrophages that constantly reside within the liver and form an effective first line defence against multiple harmful agents which reach the hepatic sinusoids via the portal circulation. KCs remove chemical compounds and dead or damaged cells, eliminate bacteria and protect against invading tumour cells. They may play a crucial tumouricidal role, exerting cytotoxic and cytostatic functions through the release of multiple cytokines and chemokines. Subsequently, colorectal metastasising cells are destroyed either by KC-performed phagocytosis or via the stimulation of other immune cells which migrate into the sinusoids and act accordingly. On the contrary, KC products, including cytokines, growth factors and matrix-degrading enzymes may promote liver metastasis, supporting tumour cell extravasation, motility and invasion. Current research aims to exploit the antineoplastic properties of KCs in new therapeutic approaches of colorectal cancer liver metastasis. Numerous agents, such as the granulocyte macrophage-colony stimulating factor, interferon gamma, muramyl peptide analogues and various antibody based treatments, have been tested in experimental models with promising results. Future trials may investigate their use in everyday clinical practice and compare their therapeutic value with current treatment of the disease. [ABSTRACT FROM AUTHOR]

The ability of the liver to regenerate after resection has been known for many years. Two reports from Germany in the late 1800s probably mark the introduction of the phenomenon into the scientific literature, but in the early 1900s the first reviews of this subject had appeared in the English literature. Predating these early scientific reports the legends from the Greek mythology described the fate of Prometheus. As punishment for defying Zeus and revealing the secret of fire to man, Prometheus was chained to a rock and each day had part of his liver ripped out by an eagle which, returning the following day, repeated the torture because his liver regenerated itself overnight. Although the speed of regeneration in the Greek legend is somewhat greater than that observed either clinically or in the laboratory, the myth does serve to emphasise the remarkable ability of the liver to repeatedly regenerate following repeated resections. This review aims to summarise the more recent literature concerning the early molecular events accompanying liver regeneration and to integrate this with the existing knowledge of this subject. [ABSTRACT FROM AUTHOR]