The role of gastrin and CCK-B/gastrin receptor in hepatocellular and pancreatic cancers

The in vitro effects of gastrin, glycine-extended gastrin, anti-gastrin antibodies and the CCK-B receptor antagonist PD135,158 were assessed on hepatoma cell lines. This study demonstrated that amidated gastrin and glycine-extended gastrin stimulated some hepatoma cell lines and that this could be abrogated by anti-gastrin agents. Tissue sections from patients with hepatocellular carcinoma, fibrolamellar carcinoma, cholangiocarcinoma as well as normal liver biopsies were assessed for expression of CCK-B receptor and gastrin isoforms. The results showed that most liver tumours express CCK-B receptor and precursor forms of gastrin. There appears to be little expression of the receptor and no expression of precursor forms of gastrin in normal liver. Tissue sections from patients with pancreatic cancer and normal pancreas were assessed for expression of CCK-B receptor and gastrin isoforms. The results showed that the normal pancreas showed no expression of receptor or gastrin isoforms except for occasional cells in the islets. The pancreatic cancer patients showed definite expression of CCK-B receptor and predominantly precursor forms of cancer. Studies were performed to identify the cellular sites of expression of the CCK-B receptor in the known CCK-B receptor bearing pancreatic acinar AR42J cells. Using immunoelectron microscopy and western blotting techniques the CCK-B receptor was shown to be expressed not only on the cell membrane, but also in the cytoplasm and nucleus of cells. In conclusion the expression of the gastrin precursor forms is most likely related to the autocrine production of gastrin by cancer cells. The nuclear expression of the receptor is a novel finding and may contribute to cellular proliferation in cancer cells. Gastrin and its receptor appear to be important in the growth of a variety of cancers and the understanding of this proliferative effect has led to the development of anti-gastrin agents now undergoing therapeutic clinical trials in gastrointestinal and pancreatic cancers.</p

REVIEW Prostate cancer and the influence of dietary factors and supplements: a systematic review

Background: Prostate cancer is the second most common cause of cancer worldwide after lung cancer. There is increasing evidence that diet and lifestyle plays a crucial role in prostate cancer biology and tumourigenesis. Prostate cancer itself represents a good model of cancer in which to look for chemopreventive agents due to the high disease prevalence, slowly progressive nature, and long latency period. Dietary agents have gained considerable attention, often receiving much publicity in the media. Aim: To review the key evidence available for potential chemopreventive nutrients. Methods: The methodology for this review involved a PubMed search from 1990 to 2013 using the key-words “diet and prostate cancer”, “nutrition and prostate cancer”, “dietary factors and prostate cancer”, “prostate cancer epidemiology”, “prostate cancer prevention”, “prostate cancer progression”. Results: Red meat, dietary fat and milk intake should be minimised as they appear to increase the risk of prostate cancer. Fruit and vegetables and polyphenols may be preventive in prostate cancer, but further studies are needed to draw more solid conclusions and to clarify their role in patients with an established diagnosis of prostate cancer. Selenium and vitamin supplements cannot be advocated for the prevention of prostate cancer and indeed higher doses may be associated with a worse prognosis. There is no specific evidence regarding benefits of probiotics or prebiotics in prostate cancer. Conclusions: From the wealth of evidence available, many recommendations can be made although more randomised control trials are required. These need to be carefully designed due to the many confounding factors and heterogeneity of the population