Colorectal cancer: advances in prevention and early detection

Colorectal cancer (CRC) is currently the fourth leading cause of cancer death worldwide. While mortality rates are in decline in most westernised countries, global estimates predict that CRC incidence rates and the overall number of CRC-related deaths are set to rise by 77% and 80%, respectively, by 2030. The development of CRC is multifactorial, and risk factors include various lifestyle, genetic, and environmental factors. It has been estimated that at least half of CRC cases could be prevented by a reduction in known modifiable lifestyle-related risk factors. Further reductions in CRC incidence and mortality can be achieved through screening, but the uptake of screening varies across different sectors of the population. This special issue comprises articles highlighting issues in the prevention, early diagnosis, and treatment of CRC

Unconventional pincer ligands and their transition metal complexes

This thesis describes investigations into unconventional pincer systems incorporating non-classical central donor groups. Direct reaction of 1,3-bis(diphenylphosphinomethyl)-2,3-dihydro-1H-1,3,2-benzodiazaborole (dppBH) with metal complexes and subsequent ligand manipulations have provided novel ruthenium and, for the first time, osmium boryl pincer complexes. The boryl complexes thus prepared have been observed to undergo various subsequent reactions involving the chloride and triphenylphosphine co-ligands to give new complexes. Further reactions of dppBH with complexes dichlorotris(triphenylphosphine)ruthenium(II) and -osmium(II) resulted in the first examples of sigma-borane pincer complexes, which represent intercepted intermediates in the B-H activation process, affording rare structural data for an osmium sigma-borane complex. The B-H bond of the ruthenium complex could be readily cleaved upon ligand manipulation, such as substitution of triphenylphosphine with the pi-acidic carbonyl and isocyanide ligands, which gave the disubstituted boryl complexes via spontaneous loss of HCl. Attempts to isolate a 1,8-diaminonaphthalene-based borane analogue of dppBH proved unsuccessful, though the compound 1,3 bis(diphenylphosphinomethyl)-2,3-dihydroperimidine (PhDHP) was obtained as a side-product in one case. Further investigations into this compound resulted in the development of a convenient one-pot synthesis, which could be extended to the cyclohexyl analogue 1,3 bis(dicyclohexylphosphinomethyl)-2,3-dihydroperimidine (CyDHP). These compounds were observed to react with various platinum group metal complexes to give novel N-heterocyclic carbene (NHC) pincer complexes via double geminal C-H activation of the central methylene group, providing the first examples of perimidine-based NHC inclusion as the central equatorial group of a pincer system. Reactions of dihydroperimidines with group 8 complexes dichlorotris(triphenylphosphine)ruthenium(II) and -osmium(II) have thus provided the novel pincer NHC complexes. However, reactions of PhDHP with dichlorotris(triphenylphosphine)ruthenium and CyDHP with less electron-rich ruthenium precursors instead gave asymmetric PNP coordinated complexes, in which C-H activation had not occurred, though this could be induced thermally in one case. Reactions of PhDHP and CyDHP with chlorotris(triphenylphosphine)rhodium(I) gave 16-electron chloro rhodium(I) NHC pincer complexes, and their reactivity was investigated via co-ligand manipulations and a preliminary catalytic study. The latter revealed that, while this complex was not particularly efficient for most of the reactions investigated, in some cases simple modifications of the co-ligands could substantially improve catalytic activity. Reactions of the pro-ligands with iridium precursors instead favoured the formation of coordinatively saturated complexes. The reaction of CyDHP with chlorobis(cyclooctene)iridium(I) dimer resulted in a dihydrido chloro iridium(III) NHC pincer complex, while reaction with chlorocarbonylbis(triphenylphosphine)iridium(I) instead afforded a sigma perimidinyl hydrido complex, resulting from oxidative addition of only one C-H bond to the metal centre. This was subsequently shown to readily form an NHC complex upon hydride abstraction. It became apparent that, upon reaction of the dihydroperimidine pro-ligands with metal complexes, carbene formation occurs more readily for electron-rich systems, otherwise resulting in either single or no C-H activation. These observations have provided some insight into the mechanism of NHC formation via chelate-assisted C-H activation of these precursors

The Impact of Epithelial Sodium Channel on Breast Cancer Cell Migration

Breast cancer is the most common cancer in New Zealand women, with the majority of breast cancer deaths being due to metastasis. This highlights the importance of identifying regulators and, thus, potential therapeutic targets, of breast cancer metastasis. Ion channel dysregulation may be crucial in cancer development via the regulation of cancer cell characteristics such as migration, invasion and proliferation. Ion channels, such as the epithelial sodium channel (ENaC), may regulate the important process for metastasis development of epithelial-mesenchymal transition (EMT), which involves a change of cell phenotype whereby cells lose their epithelial characteristics and exhibit a more migratory phenotype. There is limited research investigating the role of ENaC in breast cancer or the effect of ENaC on EMT. Therefore, the aim of this research is to investigate the role of ENaC in the migration of post-EMT breast cancer cells and the changes in mRNA levels of ENaC subunits and EMT markers. Two established forms of migration assay, Scratch and Boyden chamber, were used with two post-EMT breast cancer cell lines: BT549 and MDAMB231. Amiloride was used to block the activity of ENaC, and aldosterone was used to increase the expression of ENaC and the effect on breast cancer cell migration was observed. RT-qPCR was used to examine changes in ENaC subunit mRNA levels or markers of EMT following treatment with amiloride or aldosterone. When ENaC was blocked with amiloride, cell migration was significantly decreased in both cell lines in both scratch assays at 12 hrs (n = 4, p < 0.01). A reduction in cell migration was also observed in the Boyden chamber assay for the MDAMB231 cell line (n = 6, p < 0.05). When ENaC expression was increased with aldosterone, the two cell lines showed significantly enhanced migration ability in Boyden chamber assays (n = 8, p < 0.05). In the scratch assay, the BT549 cell line showed significantly enhanced migration at 12 hrs (n = 6, p < 0.05), whereas the MDAMB231 cell line had a reduced cell migration with aldosterone which was the same effect observed with amiloride. No noteworthy changes were observed in mRNA level of ENaC subunits or EMT markers following amiloride or aldosterone treatment. Altogether, these results indicate that ENaC has a role in the migration of breast cancer cells. The results of this project highlight ENaC as a potential therapeutic target for inhibiting the spread of breast cancer and improving the prognosis for breast cancer patients

World Alliance for Risk Factor Surveillance White Paper on Surveillance and Health Promotion

This is not a research paper on risk factor surveillance. It is an effort by a key group of researchers and practitioners of risk factor surveillance to define the current state of the art and to identify the key issues involved in the current practice of behavioral risk factor surveillance. Those of us who are the principal authors have worked and carried out research in this area for some three decades. As a result of a series of global meetings beginning in 1999 and continuing every two years since then, a collective working group of the International Union of Health Promotion and Education (IUHPE) was formed under the name World Alliance of Risk Factor Surveillance (WARFS). Under this banner the organization sought to write a comprehensive statement on the importance of surveillance to health promotion and public health. This paper, which has been revised and reviewed by established peers in the field, is the result. It provides the reader with a clear summary of the major issues that need to be considered by any and all seeking to carry out behavioral risk factor surveillance.Stefano Campostrini, David McQueen, Anne Taylor, and Alison Dal

The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition

<p>Abstract</p> <p>Background</p> <p>Aberrations in the Wnt pathway have been reported to be involved in the metastasis of prostate cancer (PCa) to bone. We investigated the effect and underlying mechanism of a naturally-occurring Wnt inhibitor, WIF1, on the growth and cellular invasiveness of a bone metastatic PCa cell line, PC3.</p> <p>Results</p> <p>The WIF1 gene promoter was hypermethylated and its expression down-regulated in the majority (7 of 8) of PCa cell lines. Restoration of WIF1 expression in PC-3 cells resulted in a decreased cell motility and invasiveness via up-regulation of epithelial markers (E-cadherin, Keratin-8 and-18), down-regulation of mesenchymal markers (N-cadherin, Fibronectin and Vimentin) and decreased activity of MMP-2 and -9. PC3 cells transfected with WIF1 consistently demonstrated reduced expression of Epithelial-to-Mesenchymal Transition (EMT) transcription factors, Slug and Twist, and a change in morphology from mesenchymal to epithelial. Moreover, WIF1 expression significantly reduced tumor growth by approximately 63% in a xenograft mouse model. This was accompanied by an increased expression of E-cadherin and Keratin-18 and a decreased expression of vimentin in tumor tissues.</p> <p>Conclusion</p> <p>These data suggest that WIF1 regulates tumor invasion through EMT process and thus, may play an important role in controlling metastatic disease in PCa patients. Blocking Wnt signaling in PCa by WIF1 may represent a novel strategy in the future to reduce metastatic disease burden in PCa patients.</p

Sampling and coverage issues of telephone surveys used for collecting health information in Australia: results from a face-to-face survey from 1999 to 2008

Background: To examine the trend of “mobile only” households, and households that have a mobile phone or landline telephone listed in the telephone directory, and to describe these groups by various socio-demographic and health indicators. Method: Representative face-to-face population health surveys of South Australians, aged 15 years and over, were conducted in 1999, 2004, 2006, 2007 and 2008 (n = 14285, response rates = 51.9% to 70.6%). Self-reported information on mobile phone ownership and usage (1999 to 2008) and listings in White Pages telephone directory (2006 to 2008), and landline telephone connection and listings in the White Pages (1999 to 2008), was provided by participants. Additional information was collected on self-reported health conditions and health-related risk behaviours. Results: Mobile only households have been steadily increasing from 1.4% in 1999 to 8.7% in 2008. In terms of sampling frame for telephone surveys, 68.7% of South Australian households in 2008 had at least a mobile phone or landline telephone listed in the White Pages (73.8% in 2006; 71.5% in 2007). The proportion of mobile only households was highest among young people, unemployed, people who were separated, divorced or never married, low income households, low SES areas, rural areas, current smokers, current asthma or people in the normal weight range. The proportion with landlines or mobiles telephone numbers listed in the White Pages telephone directory was highest among older people, married or in a defacto relationship or widowed, low SES areas, rural areas, people classified as overweight, or those diagnosed with arthritis or osteoporosis. Conclusion: The rate of mobile only households has been increasing in Australia and is following worldwide trends, but has not reached the high levels seen internationally (12% to 52%). In general, the impact of mobile telephones on current sampling frames (exclusion or non-listing of mobile only households or not listed in the White Pages directory) may have a low impact on health estimates obtained using telephone surveys. However, researchers need to be aware that mobile only households are distinctly different to households with a landline connection, and the increase in the number of mobile-only households is not uniform across all groups in the community. Listing in the White Pages directory continues to decrease and only a small proportion of mobile only households are listed. Researchers need to be aware of these telephone sampling issues when considering telephone surveys.Eleonora Dal Grande and Anne W Taylo