118 research outputs found
I-kappa-kinase-2 (IKK-2) inhibition potentiates vincristine cytotoxicity in non-Hodgkin's lymphoma
I-kappa-kinase-2 (IKK-2) inhibition potentiates vincristine cytotoxicity in non-Hodgkin\u27s lymphoma
Abstract
Background
IKK-2 is an important regulator of the nuclear factor-κB (NF-κB) which has been implicated in survival, proliferation and apoptosis resistance of lymphoma cells. In this study, we investigated whether inhibition of IKK-2 impacts cell growth or cytotoxicity of selected conventional chemotherapeutic agents in non-Hodgkin\u27s lymphoma.
Two established model systems were used; Follicular (WSU-FSCCL) and Diffuse Large Cell (WSU-DLCL2) Lymphoma, both of which constitutively express p-IκB. A novel, selective small molecule inhibitor of IKK-2, ML120B (N-[6-chloro-7-methoxy-9H-β-carbolin-8-yl]-2-methylnicotinamide) was used to perturb NF-κB in lymphoma cells. The growth inhibitory effect of ML120B (M) alone and in combination with cyclophosphamide monohydrate (C), doxorubicin (H) or vincristine (V) was evaluated in vitro using short-term culture assay. We also determined efficacy of the combination in vivo using the SCID mouse xenografts.
Results
ML120B down-regulated p-IκBα protein expression in a concentration dependent manner, caused growth inhibition, increased G0/G1 cells, but did not induce apoptosis. There was no significant enhancement of cell kill in the M/C or M/H combination. However, there was strong synergy in the M/V combination where the vincristine concentration can be lowered by a hundred fold in the combination for comparable G2/M arrest and apoptosis. ML120B prevented vincristine-induced nuclear translocation of p65 subunit of NF-κB. In vivo, ML120B was effective by itself and enhanced CHOP anti-tumor activity significantly (P = 0.001) in the WSU-DLCL2-SCID model but did not prevent CNS lymphoma in the WSU-FSCCL-SCID model.
Conclusions
For the first time, this study demonstrates that perturbation of IKK-2 by ML120B leads to synergistic enhancement of vincristine cytotoxicity in lymphoma. These results suggest that disruption of the NF-κB pathway is a useful adjunct to cytotoxic chemotherapy in lymphoma
Cancer and psychiatric diagnoses in the year preceding suicide
BACKGROUND: Patients with cancer are known to be at increased risk for suicide but little is known about the interaction between cancer and psychiatric diagnoses, another well-documented risk factor.
METHODS: Electronic medical records from nine healthcare systems participating in the Mental Health Research Network were aggregated to form a retrospective case-control study, with ICD-9 codes used to identify diagnoses in the 1 year prior to death by suicide for cases (N = 3330) or matching index date for controls (N = 297,034). Conditional logistic regression was used to assess differences in cancer and psychiatric diagnoses between cases and controls, controlling for sex and age.
RESULTS: Among patients without concurrent psychiatric diagnoses, cancer at disease sites with lower average 5-year survival rates were associated with significantly greater relative risk, while cancer disease sites with survival rates of \u3e70% conferred no increased risk. Patients with most psychiatric diagnoses were at higher risk, however, there was no additional risk conferred to these patients by a concurrent cancer diagnosis.
CONCLUSION: We found no evidence of a synergistic effect between cancer and psychiatric diagnoses. However, cancer patients with a concurrent psychiatric illness remain at the highest relative risk for suicide, regardless of cancer disease site, due to strong independent associations between psychiatric diagnoses and suicide. For patients without a concurrent psychiatric illness, cancer disease sites associated with worse prognoses appeared to confer greater suicide risk
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Interrogating networks: towards an agnostic perspective on governance research
Networks have rapidly become the dominant trope in governance theory and practice. While scholarship highlights important benefits, there has been insufficient systematic interrogation of the potential pathologies in network governance. This paper addresses the lacuna. We begin by discussing different kinds of network analysis and distinguishing the specific claims of network governance theory. We then pull together the scattered critically oriented literatures on the topic, identifying major problems with network modes of governance: hypocrisy, distrust, marketization, subjugation, antiproceduralism, fragmentation, and ‘netsploitation’. We finally argue for a more agnostic approach to governance research, capable of taking account of these pathologies and thereby putting networks in their place. This means avoiding the fetishization of particular modes of governance and giving more careful attention to the settings in which they each can be useful
‘What are you going to do, confiscate their passports?’ Professional perspectives on cross-border reproductive travel
Objective: This article reports findings from a UK-based study which explored the phenomenon of overseas travel for fertility treatment. The first phase of this project aimed to explore how infertility clinicians and others professionally involved in fertility treatment understand the nature and consequences of cross-border reproductive travel. Background: There are indications that, for a variety of reasons, people from the UK are increasingly travelling across national borders to access assisted reproductive technologies. While research with patients is growing, little is known about how ‘fertility tourism’ is perceived by health professionals and others with a close association with infertility patients. Methods: Using an interpretivist approach, this exploratory research included focussed discussions with 20 people professionally knowledgeable about patients who had either been abroad or were considering having treatment outside the UK. Semi-structured interviews were recorded, transcribed verbatim and subjected to a thematic analysis. Results: Three conceptual categories are developed from the data: ‘the autonomous patient’; ‘cross-border travel as risk’, and ‘professional responsibilities in harm minimisation’. Professionals construct nuanced, complex and sometimes contradictory narratives of the ‘fertility traveller’, as vulnerable and knowledgeable; as engaged in risky behaviour and in its active minimisation. Conclusions: There is little support for the suggestion that states should seek to prevent cross-border treatment. Rather, an argument is made for less direct strategies to safeguard patient interests. Further research is required to assess the impact of professional views and actions on patient choices and patient experiences of treatment, before, during and after travelling abroad
Study protocol: a randomized controlled trial of a computer-based depression and substance abuse intervention for people attending residential substance abuse treatment
Background: A large proportion of people attending residential alcohol and other substance abuse treatment have a co-occurring mental illness. Empirical evidence suggests that it is important to treat both the substance abuse problem and co-occurring mental illness concurrently and in an integrated fashion. However, the majority of residential alcohol and other substance abuse services do not address mental illness in a systematic way. It is likely that computer delivered interventions could improve the ability of substance abuse services to address co-occurring mental illness. This protocol describes a study in which we will assess the effectiveness of adding a computer delivered depression and substance abuse intervention for people who are attending residential alcohol and other substance abuse treatment. Methods/Design. Participants will be recruited from residential rehabilitation programs operated by the Australian Salvation Army. All participants who satisfy the diagnostic criteria for an alcohol or other substance dependence disorder will be asked to participate in the study. After completion of a baseline assessment, participants will be randomly assigned to either a computer delivered substance abuse and depression intervention (treatment condition) or to a computer-delivered typing tutorial (active control condition). All participants will continue to complete The Salvation Army residential program, a predominantly 12-step based treatment facility. Randomisation will be stratified by gender (Male, Female), length of time the participant has been in the program at the commencement of the study (4 weeks or less, 4 weeks or more), and use of anti-depressant medication (currently prescribed medication, not prescribed medication). Participants in both conditions will complete computer sessions twice per week, over a five-week period. Research staff blind to treatment allocation will complete the assessments at baseline, and then 3, 6, 9, and 12 months post intervention. Participants will also complete weekly self-report measures during the treatment period. Discussion. This study will provide comprehensive data on the effect of introducing a computer delivered, cognitive behavioral therapy based co-morbidity treatment program within a residential substance abuse setting. If shown to be effective, this intervention can be disseminated within other residential substance abuse programs. Trial registration. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000618954
Crop Updates 2005 - Farming Systems
This session covers forty four papers from different authors:
PLENARY
1. 2005 Outlook, David Stephens and Nicola Telcik, Department of Agriculture
FERTILITY AND NUTRITION
2. The effect of higher nitrogen fertiliser prices on rotation and fertiliser strategies in cropping systems, Ross Kingwell, Department of Agriculture and University of Western Australia
3. Stubble management: The short and long term implications for crop nutrition and soil fertility, Wayne Pluske, Nutrient Management Systems and Bill Bowden, Department of Agriculture
4. Stubble management: The pros and cons of different methods, Bill Bowden, Department of Agriculture, Western Australia and Mike Collins, WANTFA
5. Effect of stubble burning and seasonality on microbial processes and nutrient recycling, Frances Hoyle, The University of Western Australia
6. Soil biology and crop production in Western Australian farming systems, D.V. Murphy, N. Milton, M. Osman, F.C. Hoyle, L.K Abbott, W.R. Cookson and S. Darmawanto, The University of Western Australia
7. Urea is as effective as CAN when no rain for 10 days, Bill Crabtree, Crabtree Agricultural Consulting
8. Fertiliser (N,P,S,K) and lime requirements for wheat production in the Merredin district, Geoff Anderson, Department of Agriculture and Darren Kidson, Summit Fertilizers
9. Trace element applications: Up-front verses foliar? Bill Bowden and Ross Brennan, Department of Agriculture
10. Fertcare®, Environmental Product Stewardship and Advisor Standards for thee Fertiliser Industry, Nick Drew, Fertilizer Industry Federation of Australia (FIFA)
SOIL AND LAND MANAGEMENT
11. Species response to row spacing, density and nutrition, Bill Bowden, Craig Scanlan, Lisa Sherriff, Bob French and Reg Lunt, Department of Agriculture
12. Investigation into the influence of row orientation in lupin crops, Jeff Russell, Department of Agriculture and Angie Roe, Farm Focus Consultants
13. Deriving variable rate management zones for crops, Ian Maling, Silverfox Solutions and Matthew Adams, DLI
14. In a world of Precision Agriculture, weigh trailers are not passé, Jeff Russell, Department of Agriculture
15. Cover crop management to combat ryegrass resistance and improve yields, Jeff Russell, Department of Agriculture and Angie Roe, Farm Focus Consultants
16. ARGT home page, the place to find information on annual ryegrass toxicity on the web, Dr George Yan, BART Pty Ltd
17. Shallow leading tine (SLT) ripper significantly reduces draft force, improves soil tilth and allows even distribution of subsoil ameliorants, Mohammad Hamza, Glen Riethmuller and Wal Anderson, Department of Agriculture
PASTURE ANS SUMMER CROP SYSTEMS
18. New annual pasture legumes for Mediteranean farming systems, Angelo Loi, Phil Nichols, Clinton Revell and David Ferris, Department of Agriculture
19. How sustainable are phase rotations with Lucerne? Phil Ward, CSIRO Plant Industry
20. Management practicalities of summer cropping, Andrea Hills and Sally-Anne Penny, Department of Agriculture
21. Rainfall zone determines the effect of summer crops on winter yields, Andrea Hills, Sally-Anne Penny and David Hall, Department of Agriculture
22. Summer crops and water use, Andrea Hills, Sally-Anne Penny and David Hall, Department of Agriculture, and Michael Robertson and Don Gaydon, CSIRO Brisbane
23. Risk analysis of sorgum cropping, Andrea Hills and Sally-Anne Penny, Department of Agriculture, and Dr Michael Robertson and Don Gaydon, CSIRO Brisbane
FARMER DECISION SUPPORT AND ADOPTION
24. Variety release and End Point Royalties – a new system? Tress Walmsley, Department of Agriculture
25. Farming system analaysis using the STEP Tool, Caroline Peek and Megan Abrahams, Department of Agriculture
26. The Leakage Calculator: A simple tool for groundwater recharge assessment, Paul Raper, Department of Agriculture
27. The cost of Salinity Calculator – your tool to assessing the profitability of salinity management options, Richard O’Donnell and Trevor Lacey, Department of Agriculture
28. Climate decision support tools, Meredith Fairbanks and David Tennant, Department of Agriculture
29. Horses for courses – using the best tools to manage climate risk, Cameron Weeks, Mingenew-Irwin Group/Planfarm and Richard Quinlan, Planfarm Agronomy
30. Use of seasonal outlook for making N decisions in Merredin, Meredith Fairbanks and Alexandra Edward, Department of Agriculture
31. Forecasts and profits, Benefits or bulldust? Chris Carter and Doug Hamilton, Department of Agriculture
32. A tool to estimate fixed and variable header and tractor depreciation costs, Peter Tozer, Department of Agriculture
33. Partners in grain: ‘Putting new faces in new places’, Renaye Horne, Department of Agriculture
34. Results from the Grower group Alliance, Tracey Gianatti, Grower Group Alliance
35. Local Farmer Group Network – farming systems research opportunities through local groups, Paul Carmody, Local Farmer Group Network
GREENHOUSE GAS AND CLIMATE CHANGE
36. Changing rainfall patterns in the grainbelt, Ian Foster, Department of Agriculture
37. Vulnerability of broadscale agriculture to the impacts of climate change, Michele John, CSIRO (formerly Department of Agriculture) and Ross George, Department of Agriculture
38. Impacts of climate change on wheat yield at Merredin, Imma Farré and Ian Foster, Department of Agriculture
39. Climate change, land use suitability and water security, Ian Kininmonth, Dennis van Gool and Neil Coles, Department of Agriculture
40. Nitrous oxide emissions from cropping systems, Bill Porter, Department of Agriculture, Louise Barton, University of Western Australia
41. The potential of greenhouse sinks to underwrite improved land management in Western Australia, Richard Harper and Peter Ritson, CRC for Greenhouse Accounting and Forest Products Commission, Tony Beck, Tony Beck Consulting Services, Chris Mitchell and Michael Hill, CRC for Greenhouse Accounting
42. Removing uncertainty from greenhouse emissions, Fiona Barker-Reid, Will Gates, Ken Wilson and Rob Baigent, Department of Primary Industries - Victoria and CRC for Greenhouse Accounting (CRCGA), and Ian Galbally, Mick Meyer and Ian Weeks, CSIRO Atmospheric Research and CRCGA
43. Greenhouse in Agriculture Program (GIA), Traci Griffin, CRC for Greenhouse Accounting
44. Grains Greenhouse Accounting framework, D. Rodriguez, M. Probust, M. Meyers, D. Chen, A. Bennett, W. Strong, R. Nussey, I. Galbally and M. Howden
CONTACT DETAILS FOR PRINCIPAL AUTHOR
The Breast Cancer Family Registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer
The etiology of familial breast cancer is complex and involves genetic and environmental factors such as hormonal and lifestyle factors. Understanding familial aggregation is a key to understanding the causes of breast cancer and to facilitating the development of effective prevention and therapy. To address urgent research questions and to expedite the translation of research results to the clinical setting, the National Cancer Institute (USA) supported in 1995 the establishment of a novel research infrastructure, the Breast Cancer Family Registry, a collaboration of six academic and research institutions and their medical affiliates in the USA, Canada, and Australia. The sites have developed core family history and epidemiology questionnaires, data dictionaries, and common protocols for biospecimen collection and processing and pathology review. An Informatics Center has been established to collate, manage, and distribute core data. As of September 2003, 9116 population-based and 2834 clinic-based families have been enrolled, including 2346 families from minority populations. Epidemiology questionnaire data are available for 6779 affected probands (with a personal history of breast cancer), 4116 unaffected probands, and 16,526 relatives with or without a personal history of breast or ovarian cancer. The biospecimen repository contains blood or mouthwash samples for 6316 affected probands, 2966 unaffected probands, and 10,763 relatives, and tumor tissue samples for 4293 individuals. This resource is available to internal and external researchers for collaborative, interdisciplinary, and translational studies of the genetic epidemiology of breast cancer. Detailed information can be found at the URL http://www.cfr.epi.uci.edu/
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