Giuseppe Garcea

Role of inflammation in pancreatic carcinogenesis and the implications for future therapy.

Background: The link between inflammation and pancreatic cancer has been observed for a number of gastrointestinal neoplasms. This review examines the role of inflammation in pancreatic carcinogenesis and how it can be utilised to develop new therapies against pancreatic cancer. Methods: A literature review of Pubmed, Medline and Web of Science databases was undertaken using the key words, pancreatic cancer, inflammation, inducible nitric oxide, interleukins, pro-inflammatory cytokines, cyclooxygenase-2, NF-kappa B, reactive oxygen species, DNA adducts, lipoxygenases, chemoprevention. Results: Epidemiological evidence and molecular studies both in vitro and in vivo all support the hypothesis that inflammation plays an important in the initiation and progression of pancreatic tumours. Conclusion: Sustained damage caused by chronic inflammation may precede the onset of frank malignancy by a significant interval. As such, suppression of inflammatory changes and oxidative damage, may help delay or even prevent the inception of pancreatic neoplasia.

Molecular biomarkers of colorectal carcinogenesis and their role in surveillance and early intervention

Modern medicine is increasingly focused towards population surveillance for disease, coupled with the implementation of preventative measures applied to at-risk patients. Surveillance in colorectal cancer is limited by the cost and risk of endoscopy. Trials of putative chemopreventive agents in colorectal cancer are hampered by difficulties in following up large cohorts of patients over long periods of time to ascertain the clinical effect. Research into possible pathways of colorectal carcinogenesis has revealed a range of biological intermediates which could be used in surveillance, the identification of high risk populations and early diagnosis of cancer. The aim of this paper was to review the possible role of biomarkers in surveillance and the timing of intervention. A literature review using both Medline and Web of Science was performed from 1995 onwards using keywords: biomarkers, colorectal cancer, carcinogenesis, chemoprevention, surveillance and screening. Research has identified many potential biomarkers, such as cyclooxygenase-2 (COX-2), oxidative DNA adducts and glutathione S-transferase (GST) polymorphisms, which could be applied in a clinical setting to screen for and detect colorectal cancer. Molecular biomarkers, such as COX-2, oxidative DNA adducts and GST polymorphisms offer new prospects in the detection of early colorectal cancer, surveillance of high-risk populations and prediction of the clinical effectiveness of chemopreventive drugs. Their role could be extended into surgical surveillance for potentially operable disease and post-operative follow-up for disease recurrence. Research should be directed at assessing complementary biomarkers to increase clinical effectiveness in determining management options for patients.

Overexpression of the Nek2 Kinase in Colorectal Cancer Correlates With Beta-Catenin Relocalization and Shortened Cancer-Specific Survival

The serine/threonine kinase Nek2 (NIMA‐related kinase 2) regulates centrosome separation and mitotic progression, with overexpression causing induction of aneuploidy in vitro. Overexpression may also enable tumour progression through effects upon Akt signalling, cell adhesion markers and the Wnt pathway. The objective of this study was to examine Nek2 protein expression in colorectal cancer (CRC). Nek2 protein expression was examined in a panel of CRC cell lines using Western blotting and immunofluorescence microscopy. Nek2 and beta‐catenin expression were examined by immunohistochemistry in a series of resected CRC, as well as their matched lymph node and liver metastases, and correlated with clinicopathological characteristics. Nek2 protein expression in all CRC lines examined was higher than in the immortalised colonocyte line HCEC. Nek2 overexpression was present in 86.4% of resected CRC and was significantly associated with advancing AJCC tumour stage and shortened cancer‐specific survival. Elevated Nek2 expression was maintained within all matched metastases from overexpressing primary tumours. Nek2 overexpression was significantly associated with lower tumour membranous beta‐catenin expression and higher cytoplasmic and nuclear beta‐catenin accumulation. These data support a role for Nek2 in CRC progression and confirm potential for Nek2 inhibition as a therapeutic avenue in CRC. J. Surg. Oncol. 2014 110:828–838.

Chemoprevention of gastrointestinal malignancies

Background: u2003There has been considerable interest in the use of chemical or dietary agents to suppress or inhibit the development of tumours in the early stages of carcinogenesis. This concept is known as chemoprevention and although the potential for such agents is tremendous, evaluating their clinical benefit is beset with difficulties.

Focal Liver Ablation Techniques in Primary and Secondary Liver Tumors

Focal ablative techniques are promising tools in the treatment of unresectable primary and secondary liver tumors. Despite a lack of randomized controlled trials, early data suggest that these methods are effective and well-tolerated, with an acceptable complication rate. This chapter, an overview of established and experimental ablative methods, as well as clinical results reported thus far.