Cancer Research Uk Scientists have discovered a completely new route by which leukaemia develops, according to research published in Nature.

Scientists from the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge studied a gene called JAK2 which is faulty in many cases of leukaemia – but until now its role was not clear.

They discovered that if JAK2 is faulty, the cell’s meticulously controlled message system ‘short circuits’. As a result many genes are switched on and off inappropriately and a completely new cell signalling route by which leukaemia can develop is turned on.

The scientists found that the enzyme made by the JAK2 gene – is also located inside the cell nucleus and plays an important role to control how genetic information is used by the cell. Previously it was only known to be located on the inner surface of cells – acting as a messenger between the outside of the cell and the cell’s nucleus.

The team discovered that the JAK2 enzyme acts in the nucleus to switch on and off a number of genes. It does this by changing the structure of histones – the proteins that pack and protect DNA – and which control the behaviour of many genes. The garbled messages from the faulty JAK2 gene lead to mis-management of histones which results in catastrophic effects on the workings of a cell.

Lead author Professor Tony Kouzarides, director of the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge said: “This is a completely new route by which cancer can develop. In this exciting research we have revealed new unidentified parts of the cell’s messaging system which can become faulty and lead to leukaemia.”

In 2006, 7,237 people in the UK were diagnosed with leukaemia and the disease caused 4,350 deaths in the UK in 2007.

Professor Sir David Lane, Cancer Research UK’s chief scientist, said: “This is important research which will helps scientists find new and better ways to treat people with leukaemia.

Leukaemia can be difficult to treat because cancer cells are spread widely through the body so surgery is not an option. This makes it crucial to develop effective drugs to manage and treat the disease.

“These findings reveal a new route by which leukaemias develop – and gives scientists new opportunities to develop drugs which block it.”

Notes

*JAK2 phosphorylates hostone H3Y41 and excludes HP1?? from chromatin. Mark Dawson et al. Nature.

Source
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In diabetic patients with hypertension, ACE inhibitors reduce the risk of developing diabetes-related kidney disease, independent of their effect in lowering blood pressure, reports a study in the December Journal of the American Society of Nephrology.

“Our results clearly show that an ACE inhibitor should always be used in patients with high blood pressure and diabetes, even when they have no evidence of renal or cardiovascular disease,” comments the study’s lead author, Dr. Piero Ruggenenti of Mario Negri Institute for Pharmacological Research in Bergamo, Italy.

The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT) study included 1,204 patients with type 2 diabetes and high blood pressure. At the beginning of the study, none of the patients had any signs of kidney disease. They were randomly assigned to treatment with an ACE inhibitor, another type of blood pressure drug called a calcium channel blocker, a combination of an ACE inhibitor with a calcium channel blocker, or an inactive placebo. Rates of microalbuminuria-small amounts of the protein albumin in urine, the first sign of diabetic kidney disease-were compared between groups.

After an average of 31⁄2 years, patients who had good blood pressure control-regardless of which treatment they received-had lower rates of microalbuminuria. Patients taking the combination treatment had the greatest reduction in blood pressure and were less likely to require additional drugs to keep their blood pressure under control.

Taking an ACE inhibitor, alone or as part of the combination treatment, provided further protection against diabetic kidney disease. This was also the case for patients whose blood pressure remained high-as long as they were taking an ACE inhibitor, their microalbuminuria risk was similar to that of patients whose blood pressure was well-controlled. Dr. Ruggenenti points out, “Treatment with an ACE inhibitor was particularly important when the blood pressure was poorly controlled-as may happen in most diabetic patients with hypertension, despite the use of two, three, or even more drugs.”

About 30 percent of people with diabetes will go on to develop kidney failure, while even more may be at risk of premature death from cardiovascular disease. Eighty to ninety percent of patients with type 2 diabetes also have hypertension, a major risk factor for diabetic kidney disease. “Optimizing blood pressure control appears extremely important to reduce or prevent the risk of kidney failure or death for these patients,” says Dr. Ruggenenti.

All doctors who treat diabetes need to know about the protective benefits of ACE inhibitor treatment-especially primary care doctors who care for the vast majority of diabetic patients without kidney disease. “Early and effective treatment of hypertension is of paramount importance in people with diabetes, and ACE inhibitors should be the treatment of choice,” Dr. Ruggenenti concludes. “However, in most patients, an ACE inhibitor alone is not enough to achieve good control of arterial blood pressure-less than 130/80 mm Hg. In these patients, the doctor should also use other antihypertensive drugs, including a diuretic, in most cases, to achieve this target. Although using an ACE inhibitor is important, so is achieving the target blood pressure whenever possible.” For patients who can’t take ACE inhibitors, another class of drugs-the angiotensin II receptor antagonists-may be a valid alternative.

The ASN is a not-for-profit organization of 9,500 physicians and scientists dedicated to the study of nephrology and committed to providing a forum for the promulgation of information regarding the latest research and clinical findings on kidney diseases.

American Society of Nephrology (ASN)

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New research indicates that even small amounts of physical activity, approximately 75 minutes a week, can help improve the fitness levels for postmenopausal women who are sedentary and overweight or obese, according to a study in the May 16 issue of JAMA.

Low levels of cardiorespiratory fitness are associated with high risk of cardiovascular disease (CVD) and death, and improvements in fitness are associated with a reduction in these risks. Physical activity habits are the primary determinant of fitness in adults and changes in physical activity result in changes in fitness, according to background information in the article. However, there is a poor understanding of the relationship between levels of physical activity and the change in fitness levels.

Timothy S. Church, M.D., M.P.H., Ph.D., of the Louisiana State University System, Baton Rouge, La., and colleagues examined the effect of 50 percent, 100 percent, and 150 percent of the NIH Consensus Panel physical activity recommendations on cardiorespiratory fitness in sedentary, overweight or obese postmenopausal women with elevated blood pressure. The Panel recommends at least 30 minutes of moderate-intensity physical activity on most, preferably all, days of the week. The study included 464 sedentary, postmenopausal overweight or obese women whose body mass index ranged from 25.0 to 43.0 and whose systolic blood pressure ranged from 120.0 to 159.9 mm Hg. Enrollment took place between April 2001 and June 2005.

Participants were randomly assigned to 1 of 4 groups: 102 to the nonexercise control group, 155 to the 4-kcal/kg (400 calories), 104 to the 8-kcal/kg (800 calories), and 103 to the 12-kcal/kg (1,200 calories) per week energy-expenditure groups for the 6-month intervention period. Target training intensity was the heart rate associated with 50 percent (a modest intensity) of each woman’s peak VO2 (a measure of oxygen consumption and fitness level).

The average minutes of exercising per week were 72.2 for the 4-kcal/kg, 135.8 for the 8-kcal/kg, and 191.7 for the 12-kcal/kg per week exercise groups. Compared with the control group, the VO2abs (absolute) increased by 4.2 percent in the 4-kcal/kg, 6.0 percent in the 8-kcal/kg, and 8.2 percent in the 12-kcal/kg per week groups. There were no significant changes in systolic or diastolic blood pressure values from baseline to 6 months in any of the exercise groups vs. the control group.

“Perhaps the most striking finding of our study is that even activity at the 4-kcal/kg per week level [approximately 72 min/wk over about three days] was associated with a significant improvement in fitness compared with women in the nonexercise control group,” the authors write. “This information can be used to support future recommendations and should be encouraging to sedentary adults who find it difficult to find the time for 150 minutes of activity per week, let alone 60 minutes per day.”

(JAMA. 2007;297:2081-2091)

Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Dose-Response Relation Between Physical Activity and Fitness – Even a Little Is Good; More Is Better

In an accompanying editorial, I-Min Lee, M.B.B.S., Sc.D., of the Brigham and Women’s Hospital and Harvard Medical School, Harvard School of Public Health, Boston, comments on the study concerning physical activity levels and fitness.

“Although the trial by Church et al shows a linear dose-response relation between physical activity and improvements in physical fitness, with benefit observed beginning at 72 minutes a week of moderate activity, it is limited in its ability to provide direct answers for other patterns of physical activity. Understandably, because of cost and feasibility reasons, the trial mimicked only three physical activity patterns that can occur; in real life, there are infinitely more.”

“Although current knowledge regarding the dose-response relation between physical activity and health remains incomplete, the study by Church et al does provide important information on the dose of physical activity to improve physical fitness, a strong predictor of chronic disease and premature mortality. This may be succinctly summarized for patients and clinicians as ‘Even a little is good; more may be better!’”

(JAMA. 2007;297:2137-2138)

Please see the article for additional information, including financial disclosures, funding and support, etc.

Contact: Glen Duncan
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“Scientists have grown a whole beating heart in the laboratory, bringing the goal of growing replacement organs for humans a step closer”, The Guardian reported yesterday.
Many of the major newspapers reported on the development of the “first bioartificial heart”. Most focus on the idea that developing organs in the laboratory may signal an end to a shortage of replacement tissues for people requiring heart transplants. They go on to suggest that the technology could be applied to other organs.

The news stories are based on a laboratory study that “stripped” rat hearts of their cells, leaving a “scaffold” of the heart that was used to “re-grow” a rudimentary heart around it. As with all animal studies there is limited direct application to human health. However, the discovery that muscle cells were able to “grow” around an existing tissue skeleton sheds new light on their function and has revealed a potential new method to artificially generate heart muscle cells. As mentioned in the majority of the news reports, there is still a long way to go until a practical application is possible.

Where did the story come from?
br> Dr Harald Ott and colleagues from Harvard Medical School and the University of Minnesota carried out the research. The study was funded by departments at the University of Minnesota and was published in the peer-reviewed medical journal: Nature Medicine.

What kind of scientific study was this?

This was a laboratory study in tissue engineering, an interdisciplinary field that applies the principles of engineering and biological sciences toward the development of functional substitutes for damaged tissue.

The researchers used hearts that had been removed from the bodies of rats for this study. They “decellularised” the hearts using special equipment (called Langendorff apparatus) to pump a detergent (sodium dodecyl sulphate) through the hearts that stripped away their cellular components (including the structural elements and the DNA). What remained was a “heart matrix” or “scaffold” (essentially the framework of the heart, that consisted of collagen and other proteins).

This scaffold did not have the cells that are capable of contracting – the action that makes a heart pump blood. The researchers found that within the scaffold, the fibres making up the main heart vessels were preserved (i.e. the vessels were open and unobstructed) and the aortic valve was also able to open and close. This meant that some components of the heart had survived the detergent and were still capable of functioning to some degree.

The researchers then put the heart scaffolds into a bioreactor (which simulated the heart’s normal environment by forcing liquids in the right directions and by applying a stimulating electrical current). The heart scaffolds were then injected with purified heart muscle cells (obtained from rat embryos) and kept in the bioreactor for eight to 28 days. During the course of their experiment, the researchers performed several investigations on the tissues that resulted. They were particularly interested in how the “growing” heart regained its ability to contract and to respond to electrical signals. They also examined sections of the heart to see how and where the new heart cells were growing.

In a separate experiment, the researchers assessed whether they could also encourage growth of the cells that line the blood vessels in the heart (endothelial cells). To do this, the researchers infused endothelial cells from rat aortas (one of the main cardiac blood vessels) into the “decellularised” rat hearts. The liquid was made to continually move through the “heart” vessels and after seven days the hearts were dissected to see whether the heart chambers and vessels were regrowing their endothelial cells.

What were the results of the study?

The study has several important findings: firstly, the researchers were able to create a scaffold of the entire heart which had its vessels intact, its valves working and retained the four chamber structure of the heart. They observed that injecting embryonic heart cells into this scaffold stimulated the growth of heart cells which visibly contracted only four days after the injections. By the eighth day, the resulting cells showed response to an electrical current and function which researchers say was equivalent to 2% that of an adult rat heart (or 25% of the function of 16 week old embryos).

The “recellularisation” of the scaffold was greatest around the injection sites. They were also able to encourage the growth of cells that line the heart’s interior and its blood vessels.

What interpretations did the researchers draw from these results?

The researchers conclude that “with sufficient maturation” and further work on its vascular cells, this new organ could potentially become transplantable. They acknowledge that their study is limited to rat hearts, but they say that the approach “holds promise for virtually any solid organ”.

What does the NHS Knowledge Service make of this study?

- This laboratory study used recognised scientific methods and its findings open up a new avenue for research into the manufacture of functional heart muscle. Following a transplant, many patients face the very real possibility that the new organ will be rejected by their own body. The hope is that technologies such as that seen in this research may one day be used to manufacture a heart from the patient’s own stem cells, meaning the organ is less likely to be rejected by the patient’s body.

- Importantly, the new hearts that “re-grew” on the heart scaffolds were not transplanted into rats to see whether – even for these animals – they were functional enough to support life. Before we can draw conclusions about the value of this technology for transplantation, such studies must be conducted.

- Though the findings are exciting for the scientific community, a tissue engineering application that will directly benefit humans is some way off. The Guardian quotes an expert from the British Heart Foundation as saying, “This isn’t something we will see in man for at least a decade.”

Links to the science

Ott HC, Matthiesen TS, Goh S-K, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nature Med 2008; 13 Jan

This news comes from the National Health Service (NHS) of the UK.
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Boston Scientific
Corporation (NYSE: BSX) today announced that it has completed enrollment in
its SYNTAX clinical trial. SYNTAX is the first trial to compare the results
of drug-eluting stents with those of cardiac surgery in the most complex
patient subsets: those with de novo lesions involving all three coronary
arteries, in the left main coronary artery, or both. This randomized,
controlled clinical trial is designed to compare the 12-month outcomes of
such patients after treatment with percutaneous coronary intervention (PCI)
using the Company’s TAXUS(R) Express2(TM) paclitaxel-eluting coronary stent
system, versus the current clinical standard of coronary artery bypass
graft (CABG) surgery.

Previous studies comparing CABG and PCI have used balloon angioplasty
or bare-metal stents, or have been limited to highly selected patient
populations, excluding the type of patient enrolled in SYNTAX. In contrast,
SYNTAX allowed wide latitude in enrolling these complex patients, with the
final decision on whether to randomize a patient being made by the local
interventional cardiologist and cardiothoracic surgeon. More than 3,000
patients were enrolled at 85 sites in Europe and the United States.

Patients who were deemed eligible for both treatment options were
enrolled in the randomized arm comparing CABG to PCI, which included 1,800
patients (1,090 patients with three-vessel disease and 710 patients with
left main (LM) disease). Patients determined to be eligible for only one of
the treatment options (PCI or CABG) were enrolled in “nested” registries
tracking either CABG or PCI outcomes (more than 1,250 patients combined).
The primary endpoint is the 12-month major adverse cardiac and cerebral
event rate, which includes death, myocardial infarction, repeat
revascularization, and stroke. Results from this randomized arm will
provide important clinical information on the relative merits and risks of
CABG to PCI in treating complex patients who are eligible for both
treatment options. In addition, long-term vascular responses and the
relationship of late angiographic outcomes to clinical outcomes will be
assessed in a substudy of patients with LM disease randomized to PCI or
CABG treatment.

SYNTAX is considered a landmark study that will provide important data
regarding the use of DES in these highly complex patients, including
patients with three-vessel disease, left main coronary artery disease and
patients with diabetes mellitus. The trial’s Principal Investigators are
Professor Friedrich Mohr, M.D., Program Director of the Heart
Center/Cardiothoracic Surgery, University of Leipzig, Germany and Professor
Patrick Serruys, M.D., Ph.D., Chief of Interventional Cardiology,
Thoraxcenter-Erasmus University Rotterdam, The Netherlands.

In the United States, the TAXUS Express2 coronary stent system is
indicated for improving luminal diameter for the treatment of de novo
lesions less or equal to 28 mm in length in native coronary arteries
greater or equal to 2.5 to less than or equal to 3.75 mm in diameter. The
TAXUS stent system has not been approved in the U.S. for the treatment of
patients with multi- vessel disease, lesions in the left main coronary
artery or patients with Diabetes Mellitus. Additional information about the
TAXUS stent system is available at bostonscientific.

This press release contains forward-looking statements. Boston
Scientific wishes to caution the reader of this press release that actual
results may differ from those discussed in the forward-looking statements
and may be adversely affected by, among other things, risks associated with
new product development and commercialization, clinical trials,
intellectual property, regulatory approvals, competitive offerings,
integration of acquired companies, Boston Scientific’s overall business
strategy, and other factors described in Boston Scientific’s filings with
the Securities and Exchange Commission.

Boston Scientific is a worldwide developer, manufacturer and marketer
of medical devices whose products are used in a broad range of
interventional medical specialties. For more information, please visit:
bostonscientific.

Boston Scientific Corporation
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Standard one year Herceptin treatment provides long-term benefit to patients with high risk of recurrence

About 70% of women with locally advanced HER2-positive breast cancer were free of their disease three years after initiation of therapy when treated with Herceptin plus chemotherapy before surgery, compared to only around 50% of patients receiving pre-operative chemotherapy alone. These results from the final analysis of the NOAH (NeOAdjuvant Herceptin) phase III study will be presented today at the CTRC-AACR San Antonio Breast Cancer Symposium (SABCS). This is welcome news as patients with this early, but locally advanced breast cancer whose disease has spread to tissues around the breast such as the skin, muscle or lymph nodes generally face a high chance of recurrence and short life-expectancy.

“The positive results of the NOAH study show that starting Herceptin treatment prior to surgery offers long-term benefits to women with HER2-positive breast cancer,” said William M. Burns, CEO Division Roche Pharmaceuticals. “Herceptin continues to provide women with early breast cancer a much improved prognosis, even if their cancer has advanced locally.”

“Women with locally advanced HER2-positive breast cancer are difficult to treat” said Professor Luca Gianni from the Istituto Nazionale Tumori Milano, Milan, Italy, a leading investigator of the NOAH trial. “The results of the NOAH study imply that starting chemotherapy with one year of Herceptin should become the standard of care for women with locally advanced HER2-positive breast cancer”.

The aim of pre-surgery (neoadjuvant) therapy given to women with breast cancer is to improve the local control of the tumour to facilitate surgery. At the same time, the objective is to determine the sensitivity of the tumour towards a specific treatment. The NOAH study is the largest randomized Phase III trial evaluating the benefits of giving neoadjuvant Herceptin in combination with chemotherapy versus chemotherapy alone to women with locally advanced HER2-positive breast cancer. The results of this study demonstrate that starting Herceptin treatment prior to surgery helps shrink locally advanced breast cancer and improve long term outcomes.

About the NOAH study

The NOAH (NeOAdjuvant Herceptin) trial is a multicentre, randomised, open-label trial of 228 patients with centrally confirmed locally Advanced HER2-positive Breast Cancer (LABC), a particularly aggressive form of the disease. 115 patients received standard chemotherapy plus Herceptin (for one year) and 113 patients received chemotherapy alone before surgery. The primary end point was event-free survival (EFS), defined as the time between randomisation and disease recurrence or progression, or death from any cause. Secondary end points were pathological complete response (pCR), overall response rate (ORR), overall survival (OS) and safety.

The final NOAH phase III study results demonstrated that Herceptin plus chemotherapy improved event free survival at 3 years to 70% vs 53% with chemotherapy alone – the addition of Herceptin to chemotherapy reduced the relative risk of recurrence by about half (HR 0.56, p=0.006). In addition, Herceptin plus chemotherapy was shown to completely eradicate the tumour (a pathological complete response to treatment) in nearly twice as many patients, 39%, compared with only 20% of patients treated with chemotherapy alone (p=0.002). The overall response rate was also significantly increased (89% vs 77%, p=0.02).

About breast cancer

Breast cancer is the most common cancer among women worldwide.1 Each year more than one million new cases of breast cancer are diagnosed worldwide, and nearly 400,000 people will die of the disease annually.2

In HER2-positive breast cancer, increased quantities of the HER2 protein are present on the surface of the tumour cells. This is known as ‘HER2-positivity.’ High levels of HER2 are present in a particularly aggressive form of the disease which responds poorly to chemotherapy. Research shows that HER2-positivity affects approximately 20 percent of women with breast cancer.

About Herceptin (trastuzumab)

Herceptin is a humanised antibody, designed to target and block the function of HER2, a protein produced by a specific gene with cancer-causing potential. The mode of action of Herceptin is unique in that it activates the body’s immune system and suppresses HER2 to target and destroy the tumour. Herceptin has demonstrated unprecedented efficacy in treating both early and advanced (metastatic) HER2-positive breast cancer. Given on its own as monotherapy as well as in combination with or following standard chemotherapy, Herceptin has been shown to improve response rates, disease-free survival and overall survival while maintaining quality of life in women with HER2-positive breast cancer.

Herceptin received approval for use in the European Union for advanced (metastatic) HER2-positive breast cancer in 2000, and for early HER2-positive breast cancer in 2006. In the advanced setting, Herceptin is now approved for use as a first-line therapy in combination with paclitaxel where anthracyclines are unsuitable, as first-line therapy in combination with docetaxel, and as a single agent in third-line therapy. It is also approved for use in combination with an aromatase inhibitor for the treatment of post-menopausal patients with HER2 and hormone receptor co-positive metastatic breast cancer. In the early setting, Herceptin is approved for use following standard (adjuvant) chemotherapy.

Herceptin is currently being evaluated for treatment of HER2-positive gastric cancer through an extensive international clinical trial programme.

Herceptin is marketed in the United States by Genentech, in Japan by Chugai and internationally by Roche. Since 1998, Herceptin has been used to treat more than half a million patients with HER2-positive breast cancer worldwide.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, and is a market leader in virology. It is also active in other major therapeutic areas such as autoimmune diseases, inflammatory and metabolic disorders and diseases of the central nervous system. In 2007 sales by the Pharmaceuticals Division totalled 36.8 billion Swiss francs, and the Diagnostics Division posted sales of 9.3 billion francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invested over 8 billion Swiss francs in R&D in 2007. Worldwide, the Group employs about 80,000 people. Additional information is available on the Internet at roche.

All trademarks used or mentioned in this release are legally protected

References

1) World Health Organization, who.int/cancer/detection/breastcancer/en/

2) Ferlay J, et al., GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No.5, Version 2.0. IARCPress, Lyon, 2004.

Roche
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A study released “online first” in Cancer Causes & Control demonstrates that human papillomavirus (HPV) testing, using QIAGEN’s digene® HPV Test, improved cervical cancer control compared to routine Pap (cytology) testing among 50,000 women across Mexico, the first country in Latin America to implement a national screening program for the high-risk (HR) types of HPV that can cause cervical cancer.

The pilot study is the largest HPV primary screening demonstration performed in Latin America. Conducted as a pilot to determine the real world implementation and performance of HPV DNA testing in the Mexican national health system, the study confirmed the feasibility and effectiveness of implementing HPV testing as a cervical cancer primary screening strategy in a national population-based program.

“Population based programs using HR-HPV testing can improve cervical cancer prevention and control in Mexican and other populations where cytological screening is inadequate for detecting the precursors of cervical cancer,” concluded lead study author Dr. Eduardo Lazcano-Ponce, Executive Director of the Population Health Research Center at the National Institute of Public Health in Cuernavaca, Mexico. “Our findings offer strong evidence to justify implementation of population-based programs using HPV DNA screening.”

“Our paper provides clear evidence for expanding HPV testing more broadly in Mexico and similar countries. As a practical implementation pilot, the study was designed to have the everyday issues and problems faced by clinicians and administrators in a routine clinical setting. And even with these considerations, the study demonstrated successful implementation of a cervical cancer control strategy with HPV testing. This outcome is likely to have a broad impact in Latin America as the entire region faces a stubbornly high cervical cancer burden, and the study may well also have impact in Europe where some governments are currently in the process of implementing revised national cervical cancer screening programs,” said Dr. Attila T. Lorincz, study co-author and Professor of Molecular Epidemiology at the Wolfson Institute of Preventive Medicine in London.

The 50,159 women in the study, participating in Mexico’s IMSS social security program, received both conventional cytology and HPV DNA testing using QIAGEN’s digene HPV Test (also know as the Hybrid Capture® 2 HPV DNA Test). Results showed the clinical sensitivity of HPV DNA testing using the digene HPV Test to be more than double that of cytology, detecting 93.3% of precancerous and cancerous lesions compared to 40% for cytology. Better detection can allow for early treatment interventions, and the HPV test’s greater sensitivity can enable substantially longer screening intervals and thus provide a cost-effectiveness benefit, the study authors noted.

In middle-income countries like Mexico where health infrastructure for routine cervical cancer screening exists, but where geographical, cultural, and economic barriers prevent many women from regular Pap exams, HPV testing is a strategic alternative. “Cervical cytology screening has greatly reduced invasive cervical cancer incidence in industrialized countries. However, this approach requires repeated Pap testing at short intervals, confirmation of abnormalities by colposcopy, biopsy collection and histological confirmation in order to treat cancer precursor lesions. This kind of program is highly expensive and not affordable by many developing countries,” write Lazcano-Ponce et al. “New prevention alternatives for cervical cancer are needed, with greater sensitivity, to aid in improving cervical cancer screening…HPV testing has proven to be a highly sensitive screening tool for cervical cancer precursor lesions and has been successfully used in diverse clinical settings; clinical trials and epidemiological studies have demonstrated the suitability of testing for HR-HPV in population based programs.”

QIAGEN’s Hybrid Capture 2 HPV testing platform uses advanced molecular technology that is highly sensitive, standardized, and reliable. The test can be automated for high volume throughput, and requires fewer technical resources than cytology while yielding objective results.

“These latest findings show that implementation of HPV testing is doable and highly effective,” said Peer Schatz, Chief Executive Officer of QIAGEN. “The study provides confirmation that HPV testing can – and should – be implemented in Mexico and beyond. QIAGEN’s HPV test is already being used in the United States and Europe. The inclusion of HPV testing as a standard of care in Mexico and countries like it is an important step toward addressing cervical cancer worldwide.”

About cervical cancer and the digene HPV test

Worldwide, cervical cancer affects approximately 500,000 women annually and, after breast cancer, is the second-most-common malignancy found in women. Since the cause of cervical cancer HPV is known and women who have it can be identified, it is a highly preventable and treatable disease if women have access to organized prevention programs.

In the U.S., the digene HPV Test is approved for use together with a Pap test in women 30 years and older. In Europe, it is approved as an initial general population screening test either alone or together with a Pap test. It is also used as a follow-up to inconclusive Pap test results.

About QIAGEN

QIAGEN N.V., a Netherlands holding company, is the leading global provider of sample and assay technologies. Sample technologies are used to isolate and process DNA, RNA and proteins from biological samples such as blood or tissue. Assay technologies are used to make such isolated bio-molecules visible. QIAGEN has developed and markets more than 500 sample and assay products as well as automated solutions for such consumables. The company provides its products to molecular diagnostics laboratories, academic researchers, pharmaceutical and biotechnology companies, and applied testing customers for purposes such as forensics, animal or food testing and pharmaceutical process control. QIAGEN’s assay technologies include one of the broadest panels of molecular diagnostic tests available worldwide. This panel includes the digene HPV Test, which is regarded as a “gold standard” in testing for high-risk types of human papillomavirus (HPV), the primary cause of cervical cancer, as well as a broad suite of solutions for infectious disease testing and companion diagnostics. QIAGEN employs more than 3,500 people in over 30 locations worldwide.

Certain of the statements contained in this news release may be considered forward-looking statements within the meaning of Section 27A of the U.S. Securities Act of 1933, as amended, and Section 21E of the U.S. Securities Exchange Act of 1934, as amended. To the extent that any of the statements contained herein relating to QIAGEN’s products, markets, strategy or operating results are forward-looking, such statements are based on current expectations that involve a number of uncertainties and risks. Such uncertainties and risks include, but are not limited to, risks associated with management of growth and international operations (including the effects of currency fluctuations and risks of dependency on logistics), variability of operating results, the commercial development of the applied testing markets, clinical research markets and proteomics markets, nucleic acid-based molecular diagnostics market, and genetic vaccination and gene therapy markets, competition, rapid or unexpected changes in technologies, fluctuations in demand for QIAGEN’s, products (including fluctuations due to the level and timing of customers’ funding, budgets, and other factors), our ability to obtain regulatory approval of our infectious disease panels, difficulties in successfully adapting QIAGEN’s products to integrated solutions and producing such products, the ability of QIAGEN to identify and develop new products and to differentiate its products from competitors’ products, market acceptance of QIAGEN’s new products and the integration of acquired technologies and businesses. For further information, refer to the discussions in reports that QIAGEN has filed with, or furnished to, the U.S. Securities and Exchange Commission (SEC).

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Findings published in Diabetes Care from a 12-week, Phase IIb dose-ranging study showed that dapagliflozin, a novel, selective, sodium glucose co-transporter2 (SGLT2) inhibitor, produced clinically meaningful reductions across all key glycemic measures studied [glycosylated hemoglobin level (HbA1c), fasting plasma glucose (FPG), and postprandial plasma glucose (PPG)] in treatment-na??ve type 2 diabetes patients, compared to placebo. The study findings also showed that patients receiving dapagliflozin experienced greater reductions in body weight compared to patients on placebo. Adverse events across dapagliflozin and metformin doses were reported at a similar rate, which was somewhat higher than placebo.

Dapagliflozin is an investigational SGLT2 inhibitor currently in Phase III trials under joint development by Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN) as a once-daily therapy for the treatment of type 2 diabetes. SGLT2 inhibitors act by inhibiting the reabsorption of glucose in the kidney, thereby reducing the return of filtered glucose to the circulation.

“These data suggest that dapagliflozin, the first SGLT2 to be studied in Phase III clinical trials, may reduce important glycemic measures and facilitate weight loss in patients with type 2 diabetes,” said Elisabeth Svanberg, M.D., Ph.D., vice president, Development Lead, Bristol-Myers Squibb. “We look forward to further studies of dapagliflozin to fully understand its potential in the treatment of people with type 2 diabetes,” said William Mezzanotte, M.D., M.P.H., vice president, Global Products, AstraZeneca.

About the Study

This Phase IIb study, presented at the 2008 American Diabetes Association annual meeting, was designed to assess the efficacy and safety of dapagliflozin across a wide range of doses. The data represent findings from a prospective, randomized, double-blind, placebo-controlled, parallel-group study of 389 individuals with type 2 diabetes (ages 18-79) who were treatment-na??ve and whose HbA1c was greater than or equal to 7 percent and less than or equal to 10 percent. After a two-week lead-in phase that included diet, exercise and placebo, individuals were randomized to one of seven separate treatment arms: dapagliflozin 2.5 mg (n=59), 5 mg (n=58), 10 mg (n=47), 20 mg (n=59), 50 mg (n=56), metformin extended release 750 mg force-titrated at Week 2 to 1500 mg (n=56) or placebo (n=54), once daily for 12 weeks. Metformin was included as a positive control benchmark; no statistical comparison was made to the metformin arm.

The primary endpoint of the study compared mean HbA1c change from baseline for each dapagliflozin group versus placebo. The secondary endpoints included FPG change from baseline as compared to placebo, dose-dependent trends in glycemic efficacy, the proportion of individuals achieving the American Diabetes Association recommended HbA1c target of less than 7 percent and the change in 24-hour urinary glucose-to-creatinine ratio.

Study Results

After 12 weeks, individuals receiving dapagliflozin demonstrated a significant adjusted mean decrease in HbA1c from baseline of -0.71 percent for dapagliflozin 2.5 mg, -0.72 percent for dapagliflozin 5 mg, -0.85 percent for dapagliflozin 10 mg, -0.55 percent for dapagliflozin 20 mg and -0.90 percent for dapagliflozin 50 mg, compared to -0.18 percent for placebo (p-value at the 2.5, 5, 10 and 50 mg dose levels less than 0.001; p-value at the 20 mg dose level equal to 0.007). The adjusted mean decrease for metformin was -0.73 percent. No log-linear dose response relationship was demonstrated (P trend = 0.41).

Dapagliflozin also demonstrated a clinically meaningful adjusted mean decrease in FPG from baseline of -16 mg/dL for dapagliflozin 2.5 mg, -19 mg/dL for dapagliflozin 5 mg, -21 mg/dL for dapagliflozin 10 mg, -24 mg/dL for dapagliflozin 20 mg and -31 mg/dL for dapagliflozin 50 mg, compared to -6 mg/dL for placebo (p-value at the 2.5 mg dose level equal to 0.03; p-value at the 5 mg dose level equal to 0.005; p-value at the 10 mg dose level equal to 0.002; p-value at the 20 mg and 50 mg dose levels less than or equal to 0.001). The adjusted mean decrease for metformin was -18 mg/dL.

The percentage of individuals treated with dapagliflozin that achieved HbA1c of less than 7 percent after the 12 week treatment period was 46 percent for dapagliflozin 2.5 mg, 40 percent for dapagliflozin 5 mg, 52 percent for dapagliflozin 10 mg, 46 percent for dapagliflozin 20 mg and 59 percent for dapagliflozin 50 mg, compared to 32 percent for placebo and 54 percent for metformin. The 50 mg result was the only statistically significant result, with a p-value equal to 0.01.

Over 12 weeks, the incidence of adverse events was 59 percent for dapagliflozin 2.5 mg, 60 percent for dapagliflozin 5 mg, 68 percent for dapagliflozin 10 mg, 68 percent for dapagliflozin 20 mg and 63 percent for dapagliflozin 50 mg; the incidence of events was 54 percent for placebo and 68 percent for metformin. The percentages of the most commonly reported (greater than or equal to 10 percent in any group) adverse events for dapagliflozin 2.5 mg, 5 mg, 10 mg, 20 mg, and 50 mg doses and placebo and metformin, respectively, were: urinary tract infection [5, 9, 11, 7, 7, 6, 7], nausea [5, 7, 6, 3, 5, 6, 11], headache [7, 5, 4, 5, 2, 11, 4], and diarrhea [2, 2, 2, 7, 2, 7, 13].

The rate of reported hypoglycemic events was 7 percent for dapagliflozin 2.5 mg, 10 percent for dapagliflozin 5 mg, 6 percent for dapagliflozin 10 mg, 7 percent for dapagliflozin 20 mg and 7 percent for dapagliflozin 50 mg; the incidence of reported hypoglycemic events was 4 percent for placebo and 9 percent for metformin. There was no occurrence of confirmed hypoglycemia (symptoms of hypoglycemia with a fingerstick glucose less than or equal to 50 mg/dL).

Effects of Dapagliflozin on Weight Loss

The Phase IIb study also evaluated the potential impact of dapagliflozin-induced glucosuria on weight loss in people with type 2 diabetes, compared to placebo. These findings included data measuring changes in total body weight and body mass index over the 12-week study period.

Overall, greater percent decreases in total body weight occurred in the dapagliflozin treatment groups: -2.7 percent for dapagliflozin 2.5 mg, -2.5 percent for dapagliflozin 5 mg, -2.7 percent for dapagliflozin 10 mg, -3.4 percent for dapagliflozin 20 mg and -3.4 percent for dapagliflozin 50 mg compared to -1.2 percent for placebo and -1.7 percent for metformin.

About Type 2 Diabetes

Diabetes (diabetes mellitus) is a chronic disease in which the body does not produce or properly use insulin. Insulin is a hormone that is needed to convert sugar, starches (carbohydrates) and other nutrients into glucose, which is used as energy needed for daily life. The cause of diabetes continues to be investigated, and both genetic and environmental factors such as obesity and lack of exercise appear to play a role. Diabetes is associated with long-term complications that affect almost every part of the body. The disease may lead to blindness, heart and blood vessel disease, stroke, kidney failure, amputations, and nerve damage.

There are two primary underlying causes associated with type 2 diabetes: the body does not produce enough insulin (insulin deficiency), and the cells ignore the insulin (insulin resistance). Symptoms of type 2 diabetes develop gradually, and their onset is not as sudden as in type 1 diabetes. Symptoms may include fatigue, frequent urination, increased thirst and hunger, weight loss, blurred vision, and slow healing of wounds or sores. Some people, however, have no symptoms.

The kidneys play a key role in the overall regulation of blood glucose levels in the body. Normally, in healthy individuals, the kidneys filter a large volume of glucose and actively reabsorb virtually all of it. In patients with type 2 diabetes that have hyperglycemia, a greater amount of glucose is filtered and reabsorbed by the kidneys despite the fact that this perpetuates the hyperglycemia.

Over time, the factors that contribute to sustained hyperglycemia lead to glucotoxicity, which worsens insulin resistance and contributes to dysfunction in the beta cells of the pancreas. In this way, hyperglycemia appears to perpetuate a vicious cycle of deleterious effects that exacerbate type 2 diabetes.

Type 2 diabetes is most often associated with older age, obesity, family history of diabetes, previous history of gestational diabetes, physical inactivity and certain ethnicities. People with type 2 diabetes often are characterized with: insulin resistance, abdominal obesity, a sedentary lifestyle, having low HDL-C (“good”) cholesterol levels and high triglyceride levels and hypertension.

About SGLT2 Inhibitors

The kidney continuously filters glucose through the glomerulus; however, nearly all of this glucose is reabsorbed in a separate part of the kidney called the proximal tubule. A protein called SGLT2 is responsible for the majority of glucose reabsorption and helps the body retain glucose for it’s energy requirements. Inhibiting the activity of SGLT2 helps limit the amount of glucose that is reabsorbed and retained in the body, thereby leading to the excretion of glucose in the urine.

Bristol-Myers Squibb and AstraZeneca Partnership

Bristol-Myers Squibb and AstraZeneca entered into collaboration in January 2007 to enable the companies to research, develop and commercialize two investigational drugs for type 2 diabetes – saxagliptin and dapagliflozin. The Bristol-Myers Squibb/AstraZeneca Diabetes collaboration is dedicated to global patient care, improving patient outcomes and creating a new vision for the treatment of type 2 diabetes.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to extend and enhance human life. For more information visit bms.

About AstraZeneca

AstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and supplier for healthcare services. AstraZeneca is one of the world’s leading pharmaceutical companies with healthcare sales of US$ 31.6 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. For more information about AstraZeneca, please visit: astrazeneca.

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Endovascular aneurysm repair (EVAR) yields better results than open surgical repair (OSR) in high risk patients with similar costs, according to a one-year trial study which appears in the October issue of the Journal of Vascular Surgery, published by the Society for Vascular Surgery.

Data was collected from 342 patients who had an abdominal aortic aneurysm (AAA) of more than 5.5 centimeters and required elective AAA repair at London Health Sciences Center (LHSC), London, Ontario, Canada, where EVAR has been used since 1997. Of the 192 patients at a high risk of postoperative complications, 140 received EVAR and 52 had OSR.

In this one-year non-randomized prospective study, demographic, medical, health care resource utilization, cost and quality of life data were collected to determine incremental costs and effects associated with each of these procedures. Sensitivity analyses were conducted to extrapolate the one-year mortality results to a five-year time horizon under various assumptions regarding convergence of mortality rates and re-intervention rates (for EVAR patients only).

“Even with similar baseline characteristics, postoperative complications occurred more frequently in OSR patients at a high-risk of surgical complications,” said Dr. Guy De Rose, MD, medical director of surgical care at LHSC and an associate professor of surgery from the division of vascular surgery at the University of Western Ontario in London, Ontario, Canada. “The 30-day mortality rates were 0.7 percent for EVAR and 9.6 percent for OSR and significantly fewer EVAR patients had postoperative complications such as pulmonary edema, pneumonia or sepsis. In addition, the EVAR patients spent less time in the hospital and were less likely to be admitted to the ICU.”

Dr. De Rose noted that, despite the cost of the endograft (approximately $10,000), the total average initial costs of hospitalization for high risk EVAR and OSR patients were similar ($28,139 vs. $31,181 respectively). He added that total one-year medical and indirect costs also were similar at $34,146 vs. $34,170 respectively. At one-year, all cause mortality was statistically lower in EVAR patients (7.1% vs. 17.3%). Five-year extrapolations indicated that EVAR may be cost-effective compared to OSR in high-risk patients over the long-term.

“Our study found that EVAR was a cost-effective strategy compared to OSR in high risk patients and had lower postoperative complications and lower mortality rates,” said Dr. De Rose. He added that the quality of life experienced by the participating patients was similar between the two groups during the year following surgery.

“We are continuing to collect data on these patients and the longer-term results will provide more information regarding the cost-effectiveness of EVAR compared to OSR in high risk patients,” explained Dr. De Rose.

The LHSC collaborated with the Programs for Assessment of Technology in Health (PATH) Research Institute, St Joseph’s Healthcare Hamilton/McMaster University in Hamilton, Ontario, Canada on the current study. This study was conducted at the request of the Ontario Ministry of Health and Long-Term Care to provide evidence to the Ontario Health Technology Advisory Committee to support policy recommendations regarding the use of EVAR in Ontario.

About Journal of Vascular Surgery

Journal of Vascular Surgery provides vascular, cardiothoracic and general surgeons with the most recent information in vascular surgery. Original, peer-reviewed articles cover clinical and experimental studies, noninvasive diagnostic techniques, processes and vascular substitutes, microvascular surgical techniques, angiography and endovascular management. Special issues publish papers presented at the annual meeting of the Journal’s sponsoring society, the Society for Vascular Surgery. Visit the Journal web site at jvascsurg.

About the Society for Vascular Surgery

The Society for Vascular Surgery (SVS) is a not-for-profit society that seeks to advance excellence and innovation in vascular health through education, advocacy, research and public awareness. SVS is the national advocate for 2,600 vascular surgeons dedicated to the prevention and cure of vascular disease. Visit the web site at VascularWeb.

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The script for two research teams inducted into the American Chemical Society (ACS) scientific “hall of fame” – the ACS Heroes of Chemistry – is a tale of two pills. One team invented a medication that helps people with diabetes control their blood sugar levels. The second team invented a medicine that helps people stop smoking, an addiction that experts regard as today’s single greatest preventable cause of death worldwide.

The first team of Heroes – Nancy Thornberry, Ann Weber, Ph.D., and Joseph D. Armstrong III, Ph.D. – played key roles in discovering and developing JANUVIA® (sitagliptin), a diabetes medicine that enhances the body’s own ability to regulate blood sugar levels. JANUVIA® treats type 2 diabetes, the most common form of diabetes, affecting more than 24 million people in the United States and hundreds of millions worldwide. The trio of scientists work for Merck & Co., Inc., maker of JANUVIA®.

The second team of Heroes – Jotham Coe, Ph.D., and Brian O’Neill, Ph.D. – discovered CHANTIX® (varenicline), which is a prescription aid to smoking cessation for adults 18 and over. CHANTIX® is the first product specifically designed for smoking cessation, and at the time of its approval by the U.S. Food and Drug Administration (FDA) it was the first smoking cessation product to enter the market in almost 10 years. CHANTIX is a non-nicotine medication that helps address the physical side of quitting smoking by reducing the urge to smoke. In clinical trials, 44 percent of smokers who took CHANTIX quit smoking versus 18 percent taking a placebo during weeks 9 through 12 of treatment. Patients in these trials also received counseling.

CHANTIX is an important treatment option that has helped many smokers who want to quit. Smoking is the leading preventable cause of premature death. Coe and O’Neill work for Pfizer Inc., which makes CHANTIX®.

“The scientists behind today’s life-saving medicines and all the other products that sustain everyday life, are largely invisible to the public,” noted ACS President Joseph S. Francisco, Ph.D. “Heroes of Chemistry puts these individuals in the spotlight. It showcases the human face of chemistry, and how the hard work and creativity of these scientists transforms society, making life healthier and happier for millions of people around the world.”

The U.S. Food and Drug Administration (FDA) approved JANUVIA® in October 2006. It was the first of a family of oral medications that inhibit an enzyme, dipeptidyl peptidase 4 (DPP-4), that plays a major role in the body’s ability to use glucose, the sugar found in blood. In April 2007, the FDA approved JANUMET®, a combination of sitagliptin with metformin.

“Merck is committed to discovering and developing novel medicines and vaccines to address significant unmet medical needs. We are extraordinarily proud of these scientists for their role with JANUVIA,” said Peter S. Kim, Ph.D., who nominated Thornberry, Weber, and Armstrong. Kim is president of Merck Research Laboratories.

The FDA approved CHANTIX® in May 2006. CHANTIX® was modeled after a natural substance called cytisine that occurs in legumes and other plant substances. CHANTIX® binds to the same receptor subtype as nicotine, but causes the release of lower levels of the neurotransmitter dopamine. Dopamine is believed to be responsible for the pleasurable effects of smoking. At the same time, CHANTIX® also blocks nicotine from binding. Patients on CHANTIX experienced less urge to smoke cigarettes. The Pfizer team discovered a way to merge two compound classes into a single agent that is now available to help large numbers of smokers.

“Through May 2009, this medication has been approved in 86 countries and more than 7 million people have been prescribed CHANTIX® in the United States alone,” Rod MacKenzie, Ph.D., noted in nominating Coe and O’Neill. MacKenzie is Senior Vice President of Pfizer Inc. and Head of Worldwide Research for PharmaTherapeutics R&D. Worldwide sales in 2009 totaled $700 million, he said.

“The annual healthcare burden for smoking related cancers, cardiovascular disease, and respiratory disorders in the U.S. is estimated at $167 billion,” MacKenzie said. “Varenicline provides a targeted, safe and effective method to positively impact this unnecessary burden on society.”

Notes:
The 2010 Heroes of Chemistry were honored on Aug. 22 in Boston during the 240th National Meeting of the ACS, the world’s largest scientific society. The ceremony included a keynote speech by Mark Plotkin, Ph.D., renowned ethnobotanist and best-selling author of Tales of a Shaman’s Apprentice and The Killers Within: The Deadly Rise of Drug-Resistant Bacteria. He is an expert on rainforest ecosystems.

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