News Article | March 22, 2017
Laboratory Design (LD): How did you get into your field? David Keenan (DK): In an un-conventional way. I studied Zoology at University in the U.K., after which I joined a wine company that sent me to Edinburgh. After a couple of years, I realized I wanted to get back into science and found myself at the Medical Research Council’s Human Genetics Unit in Edinburgh working in a lab looking into the genetic disorders of muscle disease. The lab was successful and my boss was recruited to Sydney. He invited me to join him, so I left the U.K. to move to Australia, where I took on the role of setting up the lab and aquarium at the Victor Chang Cardiac Research Institute in Sydney. I thoroughly enjoyed this and it led to my next job, at the Garvan Institute. Over time I became responsible for planning and delivering larger and larger research buildings. My last project was the Victorian Comprehensive Cancer Center, a large $1 billion Public Private Partnership mixed health and research facility in Melbourne. I’ve now found my way to HDR. LD: What’s the most surprising thing you’ve learned in your career? DK: How close many door frames are to the height of a ULT-80 freezer, or how wide a double door is for a pallet movement/large piece of equipment. It is important to consider the items moving through any given door and, in particular, the full travel path for some large items to ensure usefulness and flexibility of the space. LD: What’s a common mistake made by those working on designing/constructing a laboratory? DK: The movement of materials and people through a lab is often not considered fully or in all situations. I’ve seen ramps in places where heavy loads are moved, or a single elevator at one end of a building that might often be on exclusive use. Then there are the issues of moving biological materials through non-lab environments to get from point A to B: Do you wear gloves or not, gowns or not; double-bag or not; are you traversing where people might eat/drink; and so on. These are all issues to be carefully considered in planning out how the spaces will be used. LD: What do you consider the highlight of your career? DK: It’s a tough pick but the Kinghorn Cancer Centre is a beautiful facility that is planned to be both functionally simple and, in my opinion, ‘elegant.’ The Victorian Comprehensive Cancer Centre is a close second for the sheer scale and challenge—everything about it was big! LD: If you could give just one piece of advice to others in your field, what would it be? LD: Can you describe a funny or exciting moment in your career? DK: A very exciting AND scary moment in my career had to be when we unveiled the Richard Long (U.K. Turner Prize-winning artist) artwork in the Kinghorn Cancer Centre. The artwork is a chalk mix on painted concrete that is eight stories high: spectacular in both scale and impact. There was a heart-stopping moment when a leak appeared during a freak torrential storm immediately after occupancy. Water tracked to just above the piece and began to run down the middle of the artwork … thankfully we repaired the leak immediately and the art wasn’t damaged but it was a scary time! LD: Is there anything else you’d like to share with the readers of Laboratory Design? DK: Don’t take yourself too seriously.
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.
PubMed | Western University of Health Sciences, Greater Southern Area Health Service and East Hume Border Clinical Network, Peninsula Health, Bendigo Health and 8 more.
Type: Journal Article | Journal: Internal medicine journal | Year: 2016
These guidelines, informed by the best available evidence and consensus expert opinion, provide a framework to guide the timely initiation of chemotherapy for treating cancer. They sit at the intersection of patient experience, state-of-the-art disease management and rational efficient service provision for these patients at a system level. Internationally, cancer waiting times are routinely measured and publicly reported. In Australia, there are existing policies and guidelines relating to the timeliness of cancer care for surgery and radiation therapy; however, until now, equivalent guidance for chemotherapy was lacking. Timeliness of care should be informed, where available, by evidence for improved patient outcomes. Independent of this, it should be recognised that shorter waiting periods are likely to reduce patient anxiety. While these guidelines were developed as part of a proposed framework for consideration by the Victorian Department of Health, they are clinically relevant to national and international cancer services. They are intended to be used by clinical and administrative staff within cancer services. Adoption of these guidelines, which are for the timely triage, review and treatment of cancer patients receiving systemic chemotherapy, aims to ensure that patients receive care within a timeframe that will maximise health outcomes, and that access to care is consistent and equitable across cancer services. Local monitoring of performance against this guideline will enable cancer service providers to manage proactively future service demand.
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.
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.
Roberts A.W.,Royal Melbourne Hospital |
Roberts A.W.,Walter and Eliza Hall Institute of Medical Research |
Roberts A.W.,Victorian Comprehensive Cancer Center |
Roberts A.W.,University of Melbourne |
And 21 more authors.
New England Journal of Medicine | Year: 2016
BACKGROUND: New treatments have improved outcomes for patients with relapsed chronic lymphocytic leukemia (CLL), but complete remissions remain uncommon. Venetoclax has a distinct mechanism of action; it targets BCL2, a protein central to the survival of CLL cells. METHODS: We conducted a phase 1 dose-escalation study of daily oral venetoclax in patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL) to assess safety, pharmacokinetic profile, and efficacy. In the dose-escalation phase, 56 patients received active treatment in one of eight dose groups that ranged from 150 to 1200 mg per day. In an expansion cohort, 60 additional patients were treated with a weekly stepwise ramp-up in doses as high as 400 mg per day. RESULTS: The majority of the study patients had received multiple previous treatments, and 89% had poor prognostic clinical or genetic features. Venetoclax was active at all dose levels. Clinical tumor lysis syndrome occurred in 3 of 56 patients in the dose-escalation cohort, with one death. After adjustments to the dose-escalation schedule, clinical tumor lysis syndrome did not occur in any of the 60 patients in the expansion cohort. Other toxic effects included mild diarrhea (in 52% of the patients), upper respiratory tract infection (in 48%), nausea (in 47%), and grade 3 or 4 neutropenia (in 41%). A maximum tolerated dose was not identified. Among the 116 patients who received venetoclax, 92 (79%) had a response. Response rates ranged from 71 to 79% among patients in subgroups with an adverse prognosis, including those with resistance to fludarabine, those with chromosome 17p deletions (deletion 17p CLL), and those with unmutated IGHV. Complete remissions occurred in 20% of the patients, including 5% who had no minimal residual disease on flow cytometry. The 15-month progression-free survival estimate for the 400-mg dose groups was 69%. CONCLUSIONS: Selective targeting of BCL2 with venetoclax had a manageable safety profile and induced substantial responses in patients with relapsed CLL or SLL, including those with poor prognostic features. Copyright © 2015 Massachusetts Medical Society.
Khaw S.L.,Walter and Eliza Hall Institute of Medical Research |
Khaw S.L.,University of Melbourne |
Khaw S.L.,Royal Childrens Hospital |
Merino D.,Walter and Eliza Hall Institute of Medical Research |
And 14 more authors.
Leukemia | Year: 2014
Overexpression of the prosurvival protein Bcl-2 marks many B-lymphoid malignancies and contributes to resistance to many commonly used chemotherapeutic agents. The first effective BH3 mimetic inhibitors of Bcl-2, ABT-737 and navitoclax, also target Bcl-x L, causing dose-limiting thrombocytopenia. This prompted the development of the Bcl-2-selective antagonist, ABT-199. Here we show that in lymphoid cells, ABT-199 specifically causes Bax/Bak-mediated apoptosis that is triggered principally by the initiator BH3-only protein Bim. As expected, malignant cells isolated from patients with chronic lymphocytic leukaemia are highly sensitive to ABT-199. However, we found that normal, untransformed mature B cells are also highly sensitive to ABT-199, both in vitro and in vivo. By contrast, the B-cell precursors are largely spared, as are cells of myeloid origin. These results pinpoint the probable impact of the pharmacological inhibition of Bcl-2 by ABT-199 on the normal mature haemopoietic cell lineages in patients, and have implications for monitoring during ABT-199 therapy as well as for the clinical utility of this very promising targeted agent. © 2014 Macmillan Publishers Limited.
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.
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.
PubMed | Cancer Institute NSW, Victorian Comprehensive Cancer Center and University of Sydney
Type: Evaluation Studies | Journal: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco | Year: 2015
The Australian states of New South Wales (NSW) and Queensland implemented bans on tobacco pack displays at point-of-sale (PoS) in July 2010 and November 2011, respectively. This study evaluated the medium-term impact of the bans on youth.Data were drawn from the Tobacco Promotion Impact Study, a repeated cross-sectional survey of youth (12-24 years) in NSW and Queensland conducted yearly 2010-2012 (n = 6,014). Regression analyses examined differences in youths recall of PoS tobacco displays, smoking-related beliefs, and smoking behaviors in relation to the timing of the PoS display bans.Recall of PoS tobacco displays was significantly less likely for youth interviewed after the bans versus before (OR = 0.45, 95% CI = 0.39, 0.52, p < .01). They were also less likely to report tobacco brand awareness (OR = 0.76, 95% CI = 0.62, 0.92, p < .01), to over-estimate peer smoking (OR = 0.84, 95% CI = 0.74, 0.96, p < .01), or be current smokers (OR = 0.73, 95% CI = 0.55, 0.96, p < .05). Stratified analyses showed that these differences were primarily apparent in the group of youth most likely to be affected by tobacco PoS displays: those who visit tobacco retailers most frequently. After the bans, smokers were less likely to report that they think about smoking as a result of seeing PoS tobacco displays (OR = 0.60, 95% CI = 0.37, 0.97, p < .039).Our findings suggest an immediate impact of display bans on youths exposure to tobacco pack displays, and likely impacts on smoking-related outcomes. These results suggest that removing tobacco displays from retail environments can positively contribute to the denormalization of smoking among youth.