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Ernst M.,Ludwig Institute for Cancer Research | Ernst M.,Victorian Comprehensive Cancer Center | Ramsay R.G.,University of Melbourne | Ramsay R.G.,Victorian Comprehensive Cancer Center
Journal of Gastroenterology and Hepatology (Australia) | Year: 2012

Sequences of molecular events that initiate and advance the progression of human colorectal cancer (CRC) are becoming clearer. Accepting that these events, once they are in place, accumulate over time, rapid disease progression might be expected. Yet CRC usually develops slowly over decades. Emerging insights suggest that the tumor cell microenvironment encompassing fibroblasts and endothelial and immune cells dictate when, whether, and how malignancies progress. Signaling pathways that affect the microenvironment and the inflammatory response seem to play a central role in CRC. Indeed, some of these pathways directly regulate the stem/progenitor cell niche at the base of the crypt; it now appears that the survival and growth of neoplastic cells often relies upon their subverted engagement of these pathways. Spurned on by the use of gene manipulation technologies in the mouse, dissecting and recapitulating these complex molecular interactions between the tumor and its microenvironment in the gastrointestinal (GI) tract is a reality. In parallel, our ability to isolate and grow GI stem cells in vitro enables us, for the first time, to complement reductionist in vitro findings with complex in vivo observations. Surprisingly, data suggest that the large number of signaling pathways underpinning the reciprocal interaction between the neoplastic epithelium and its microenvironment converge on a small number of common transcription factors. Here, we review the separate and interactive roles of NFκB, Stat3, and Myb, transcription factors commonly overexpressed or excessively activated in CRC. They confer molecular links between inflammation, stroma, the stem cell niche, and neoplastic cell growth. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.


Bishop J.F.,Victorian Comprehensive Cancer Center | Bishop J.F.,University of Melbourne
Cancer Forum | Year: 2013

Haematological malignancies have identified the path forward for oncology, initially with systemic treatment and combination chemotherapy and limiting the need for or extent of radiotherapy. In recent years, important targeted therapies were first demonstrated as practical with the first tyrosine kinase inhibitors, the first monoclonal antibodies and the extensive genetic characterisation and classification of these diseases. The genomic era holds the promise of further, more rapid progress, with remaining intractable problems such as poor outcomes overall with acute myeloid leukaemia, both primary and secondary, and possibly new therapy that could avoid the short and long-term sideeffects of curative chemotherapy. The extensive sub-classification of leukaemia and lymphoma into smaller sub-sets have made some large scale clinical trials a challenge and may have flagged an emerging obstacle to progress in cancer trials more generally.


Perez D.,Cancer Institute NSW Cancer Screening and Prevention | Kite J.,University of Sydney | Dunlop S.M.,Cancer Institute NSW Cancer Screening and Prevention | Cust A.E.,University of Sydney | And 5 more authors.
Health Education Research | Year: 2015

Melanoma is the most common cancer among 15- to 29-year-olds in Australia, with rates increasing with age. The 'Dark Side of Tanning' (DSOT) mass media campaign was developed in 2007 to influence attitudes related to tanning. This study aimed to assess recall and impact of the DSOT campaign. Data were collected using online surveys of 13- to 44-year-olds living in New South Wales in the summer months of 2007-2010 (n = 7490). Regression models were used to determine predictors of recall of DSOT and to investigate associations between exposure to the campaign and tanning attitudes. The campaign achieved consistently high recall (unprompted recall 42-53% during campaign periods; prompted recall 76-84%). Those who recalled DSOT advertisements had a higher likelihood of reporting negative tanning attitudes compared with those who reported no recall, after adjusting for other factors (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.01-1.27 for unprompted recall; OR 1.19, 95% CI 1.03-1.36 for prompted recall). Being interviewed in later campaign years was also a significant predictor of negative tanning attitudes (e.g. fourth year of campaign versus first year: OR 1.24, 95% CI 1.01-1.53). These results suggest that mass media campaigns have potential to influence tanning-related attitudes and could play an important role in skin cancer prevention. © 2015 The Author 2015. Published by Oxford University Press. All rights reserved.


Trapani J.A.,Research Division | Trapani J.A.,University of Melbourne | Trapani J.A.,Victorian Comprehensive Cancer Center
Cell Death and Differentiation | Year: 2012

Within the powerful legacy left by Jurg Tschopp, we should not forget his early work that helped to elucidate the molecular pathways responsible for the clearance of virus-infected and transformed cells by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. Jurg's skilful biochemical approach formed a firm platform upon which the work of so many other biochemists, cell biologists and immunologists would come to rely. Jurg coined the shorthand term granzyme to denote the individual members of a family of serine proteases sequestered in and secreted from the cytotoxic granules of CTL/NK cells. He was also one of the first to describe the lytic properties of purified perforin and to postulate the synergy of perforin and granzymes, which we now know to underpin target cell apoptosis. Jurg was a major protagonist in the debate that raged throughout the 1980's and early 1990's on the physiological relevance of the granule exocytosis pathway. Ultimately, resolving this issue led Jurg and his colleagues to even greater and impactful discoveries in the broader field of apoptosis research. Jurg Tschopp ranks with other pioneers, particularly Gideon Berke, Chris Bleackley, Pierre Golstein, Pierre Henkart and Eckhard Podack for making seminal discoveries on our understanding of how the immune system eliminates dangerous cells. © 2012 Macmillan Publishers Limited All rights reserved.


Dunlop S.M.,University of Sydney | Dunlop S.M.,Cancer Institute NSW | Perez D.,Cancer Institute NSW | Cotter T.,Victorian Comprehensive Cancer Center
Tobacco Control | Year: 2014

Background The necessary first steps for televised media campaign effects are population exposure and recall. To maximise the impact of campaign funding, it is critical to identify modifiable factors that increase the efficiency of an advertisement reaching the target audience and of their recalling that advertisement. Methods Data come from a serial cross-sectional telephone survey with weekly interviews of adult smokers and recent quitters from the state of New South Wales, Australia, collected between April 2005 and December 2010 (total n=13 301). Survey data were merged with commercial TV ratings data (Gross Rating Points (GRPs)) to estimate individuals' exposure to antismoking campaigns. Results Multivariable logistic regression analyses indicated that GRPs and broadcasting recency were positively associated with advertisement recall, such that advertisements broadcast more at higher levels or in more recent weeks were more likely to be recalled. Advertisements were more likely to be recalled in their launch phase than in following periods. Controlling for broadcasting parameters, advertisements higher in emotional intensity were more likely to be recalled than those low in emotion; and emotionally intense advertisements required fewer GRPs to achieve high levels of recall than lower emotion advertisements. There was some evidence for a diminishing effect of increased GRPs on recall. Conclusions In order to achieve sufficient levels of population recall of antismoking campaigns, advertisements need to be broadcast at adequate levels in relatively frequent cycles. Advertisements with highly emotional content may offer the most efficient means by which to increase population recall.

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