LRCTC News - June 2011
The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy
30 June 2011
Andrew F. Reada,b,1, Troy Dayc, and Silvie Huijbena Proceedings of the National Academy of Sciences of USA (PNAS)June 20, 2011
Abstract
The evolution of drug-resistant pathogens is a major challenge for 21st century medicine. Drug use practices vigorously advocated as resistance management tools by professional bodies, public health agencies, and medical schools represent some of humankind's largest attempts to manage evolution. It is our contention that these practices have poor theoretical and empirical justification for a broad spectrum of diseases. For instance, rapid elimination of pathogens can reduce the probability that de novo resistance mutations occur. This idea often motivates the medical orthodoxy that patients should complete drug courses even when they no longer feel sick. Yet “radical pathogen cure” maximizes the evolutionary advantage of any resistant pathogens that are present. It could promote the very evolution it is intended to retard. The guiding principle should be to impose no more selection than is absolutely necessary. We illustrate these arguments in the context of malaria; they likely apply to a wide range of infections as well as cancer and public health insecticides. Intuition is unreliable even in simple evolutionary contexts; in a social milieu where in-host competition can radically alter the fitness costs and benefits of resistance, expert opinion will be insufficient. An evidence-based approach to resistance management is required
Nobel Prize Winner to Test Cancer-Causing Bug in Drinkable Flu Vaccine
30 June 2011
By Simeon Bennett - Jun 28, 2011 3:00 PM GMT+0100 .
Barry J. Marshall, the Australian scientist who won a Nobel Prize for identifying a cancer-causing stomach bacterium, plans to start a trial next year using the bug in a drinkable flu vaccine.
Marshall, the founder, scientific director and majority owner of closely held Ondek Ltd., plans to test the vaccine in at least 30 people in the U.S., and expects results from the trial by mid-2013, he said in a telephone interview yesterday.
Ondek, based in Perth, Australia, aims to harness the ability of the bacterium Helicobacter pylori to colonize the stomach. The bug’s harmful genes will be removed and those from influenza and other viruses will be inserted to stimulate an immune response. If successful, the vaccine would be sold as a freeze-dried powder or a capsule, sidestepping the inconvenience and side effects of injections, Marshall said.
“We’re focusing on flu because we think that would be attractive to investors,” Marshall said. “That’s the big market.”
A preliminary study, in which healthy volunteers received disarmed strains of the bacterium in a beef broth, showed some strains were capable of safely colonizing the gut, proving the concept is feasible, Marshall said. The strains weren’t carrying any viral genes. He presented the results at a conference in Singapore on June 23.
The flu-vaccine market reached about $3.7 billion last year, Ondek said on its website. The company, which has about 20 investors, has raised more than A$3 million ($3.1 million) of a targeted A$5 million for the next trial and is seeking more funding, Marshall said.
“In Australia people are more comfortable with mining investments and will put massive amounts of money into holes in the ground,” he said. “We don’t have a lot of mature investors yet who’ve had a good experience in biotechnology, and can see that it’s a similar type of risk-benefit ratio.”
Increasing rates of cervical cancer in young women in England
30 June 2011
16 June 2011 : Interrogation of a UK national cancer registration database has revealed a significant increase in cervical cancer rates in 20-29 year-olds in the period 1992-2006.
http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2011196a.html
Formaldehyde substitute fixatives: effects on nucleic acid preservation
30 June 2011
Cathy B Moelans, Daphne Oostenrijk, Michiel J Moons, Paul J van Diest Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands J Clin Pathol doi:10.1136/jclinpath-2011-200152
Abstract
Aims In surgical pathology, formalin-fixed paraffin-embedded tissues are increasingly being used as a source of DNA and RNA for molecular assays in addition to histopathological evaluation. However, the commonly used formalin fixative is carcinogenic, and its crosslinking impairs DNA and RNA quality.
Methods The suitability of three new presumably less toxic, crosslinking (F-Solv) and non-crosslinking (FineFIX, RCL2) alcohol-based fixatives was tested for routine molecular pathology in comparison with neutral buffered formalin (NBF) as gold standard. Size ladder PCR, epidermal growth factor receptor sequence analysis, microsatellite instability (MSI), chromogenic (CISH), fluorescence in situ hybridisation (FISH) and qPCR were performed.
Results The alcohol-based non-crosslinking fixatives (FineFIX and RCL2) resulted in a higher DNA yield and quality compared with crosslinking fixatives (NBF and F-Solv). Size ladder PCR resulted in a shorter amplicon size (300 bp) for both crosslinking fixatives compared with the non-crosslinking fixatives (400 bp). All four fixatives were directly applicable for MSI and epidermal growth factor receptor sequence analysis. All fixatives except F-Solv showed clear signals in CISH and FISH. RNA yield and quality were superior after non-crosslinking fixation. qPCR resulted in lower Ct values for RCL2 and FineFIX.
Conclusion The alcohol-based non-crosslinking fixatives performed better than crosslinking fixatives with regard to DNA and RNA yield, quality and applicability in molecular diagnostics. Given the higher yield, less starting material may be necessary, thereby increasing the applicability of biopsies for molecular studies.
An investigation of adequate volume for the diagnosis of malignancy in pleural fluids
30 June 2011
S. C. Thomas, L. R. R. Davidson, M. E. McKean Cytopathology Volume 22, Issue 3, pages 179–184, June 2011
Objective: The cytological examination of pleural effusions is an important investigation in the diagnosis of malignancy. Maximizing the chances of identifying malignant effusions is therefore desirable. Recent Royal College of Pathologists guidelines, based on the British Society for Clinical Cytology codes of practice, have suggested that a minimum of 20 ml of pleural fluid is required for diagnostic purposes.
Methods & Results: We examined 2155 pleural fluids received over a 6-year period in order to define a minimum required volume for adequacy. By examining the plateau phase of a graph of threshold volumes for initial samples received for each patient (n = 1584) we determine that a minimum fluid volume of 25 ml is required and that more than 50 ml does not improve sensitivity.
Conclusion: Between 25 and 50 ml of fluid are required for the adequate assessment of pleural effusions for malignancy.
View article...
Profile of Cervical Cancer in England Report - February 2011
08 June 2011
The National Cancer Intelligence Network and the NHS Cervical Screening Programme have produced a collaborative report detailing the current status of cervical cancer in England.
A word on HPV Vaccines
08 June 2011
Cervarex (bivalent 16,18) was a bad decision claim sexual health experts.
Dismay at UK government not choosing Gardasil quadrivalent vaccine.
Cervarex does not protect against genital warts caused by HPV subtypes 6 & 11
In contrast Australia chose Gardasil has seen a 47% drop in genital warts since immunisation began (UK spends circa £25 million pa on treatment warts)
February 2011 www.bbc.co.uk/cancer/news/health
NHS Cancer Screening Programme
08 June 2011
15th December 2010 DOH published the NHS Operating Framework. It recommends HPV Triage (Low grades only) to be rolled out across England- London has set up a working party for a planned roll out.
Cytology 14 day TAT
08 June 2011
12th January 2011 Cancer Strategy-Improving Outcomes: section 4.25 “November 2010 81% women were receiving their results within 14 days. As recommended by the Advisory Committee on Cervical Screening (ACCS) the threshold for achieving this has been set at 98%” Average cost saving of £100,000 saved per unit per year.