الثلاثاء، 8 نوفمبر 2011

Genetic Mutations Associated With Increased PSA And Prostate Cancer

Austrian researchers have uncovered mutations throughout the mitochondrial genome that are associated with prostate cancer. An exciting aspect of the study, published by Cell Press in the American Journal of Human Genetics, is the association of tRNA mutations with elevated levels of prostate-specific antigen (PSA) in Austrian men diagnosed with various stages of prostate cancer.



Prostate cancer is among the most prevalent cancers diagnosed in the United States and Europe. The most common and noninvasive way to detect prostate cancer is to check PSA levels. This is a routine part of men's health checks starting around the age of 50. Elevated PSA levels indicate the possibility of prostate cancer. Prostate biopsies are used for verification of PSA results and cancer diagnosis. Treatment may include surgery, radiation, or chemotherapy. "Identifying genetic variants associated with prostate cancer and its primary biomarker is an exciting accomplishment," says Dr. Anita Kloss-Brandst?¤tter, the lead author of this study.



Recognizing the important role mtDNA mutations have been found to play in development and progression of many types of cancer, Dr. Kloss-Brandst?¤tter and colleagues set out to sequence the entire mitochondrial genome in 30 prostate cancer patients. "The influence of mtDNA on the origin and progression of prostate cancer is still not understood, leaving much to be discovered," says Dr. Kloss-Brandst?¤tter. The group used a high-quality sequencing approach to detect differences in mtDNA sequence between cancerous and noncancerous tissue from the same 30 men. "It is the first study targeting the entire mitochondrial genome in prostate cancer and benign tissue from the same patient with a superior sequencing strategy," notes Dr. Kloss-Brandst?¤tter.



By examining both the frequency and types of somatic mtDNA mutations in prostate cancer patients, Dr. Kloss-Brandst?¤tter and colleagues were able to identify several genetic changes having clinical significance. They suggest that, "sequencing of selected mitochondrial regions will likely result in a mutation spectrum useful for prognosis." Perhaps the most striking finding of the study is the association between somatic tRNA mutations and PSA levels at diagnosis. "Patients with a somatic tRNA mutation had a significantly higher PSA value at diagnosis than did patients without a somatic tRNA mutation," explains Dr. Kloss-Brandst?¤tter. "These findings will potentially help others monitor malignant transformation, tumor progression, and metastasis," she says.



Source:

Elisabeth (Lisa) Lyons

Cell Press

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Gastric Bypass Surgery Restores Sexual Function In Morbidly Obese Men

Losing weight may help resolve erectile dysfunction in obese men, according to research presented at the 103rd Annual Scientific Meeting of the American Urological Association (AUA). Morbid obesity can cause sexual dysfunction independent of other common confounders, including diabetes, hypertension and smoking. In this study from researchers in Boston and Philadelphia, sexual function was normalized in some men who underwent gastric bypass surgery for weight loss. Researchers will present data to reporters during a special press conference on May 19, 2008 at 10:30 a.m.


"This study shows that weight loss and other risk factors which are alleviated by weight loss may be keys to restoring sexual function," said Anthony Y. Smith, M.D. "These results give men another reason to improve their health by losing weight."


In this study, 95 patients undergoing gastric bypass surgery for weight loss completed the Brief Sexual Inventory (BSI) pre- and post-operatively. On average, BSI scores improved in all categories, including sexual drive, erectile function, ejaculatory function, problem assessment and sexual satisfaction. The amount of weight lost predicted the degree of improvement in all areas of the survey. Results were then compared to data from the Olmstead County Study of Urinary Health Status Survey, a community-based prospective study often used as a baseline for study comparison. After an average of 67 percent weight loss post-bypass, BSI scores were comparable to patients in the Olmstead Study.


Gastric bypass surgery, a procedure that reduces the body's caloric intake, can be used to induce significant weight loss in the obese. Calorie reduction is accomplished by making the stomach smaller and bypassing part of the stomach and small intestines so that fewer calories are absorbed. The patient feels full faster and learns to reduce the amount of food that he/she eats.


In addition to the author, Anthony Y. Smith, M.D., a member of the AUA Public Media Committee, will be on hand to answer questions and provide third-party perspective on the study.


Dallal Rm, Smith JA, O'Leary MP, Harkaway RC, Sawh SL: Profound sexual dysfunction is common in the morbidly obese male and is reversed after gastric bypass surgery. J Urol, suppl., 2008; 179:405, abstract 1178.


About the American Urological Association: Founded in 1902 and headquartered near Baltimore, Maryland, the American Urological Association is the pre-eminent professional organization for urologists, with more than 15,000 members throughout the world. An educational nonprofit organization, the AUA pursues its mission of fostering the highest standards of urologic care by carrying out a wide variety of programs for members and their patients, including UrologyHealth, an award-winning on-line patient education resource, and the American Urological Association Foundation, Inc.


American Urological Association (AUA)

1000 Corporate Blvd.

Linthicum, MD 21040

United States

auanet


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NICE Recommends Two New Cancer Drugs This Month

In final guidance published today, NICE is pleased to be able to recommend two new treatments; for inoperable advanced gastric cancer and for non small cell lung cancer.


Capecitabine (Xeloda, Roche Products) is recommended, in combination with a platinum-based regimen, for the first-line treatment of inoperable advanced gastric cancer and gefitinib (Iressa) is recommended for the first-line treatment of people with locally advanced or metastatic non-small-cell lung cancer if they test positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation.


Dr Carole Longson, Health Technology Evaluation Centre Director at NICE said: "NICE has already recommended a number of treatments for non small lung cancer. Gefitinib has now been added to this list of treatment options, with the advantage that it is taken in tablet form, meaning it can be taken at home, and would allow patients to carry on with normal daily activities


"Before today patients with inoperable advanced gastric cancer were generally treated with fluorouracil via an infusion pump. However, capecitabine-based regimens work as well as intravenous fluorouracil and because the treatment is with tablets, rather than an infusion pump, patients will spend less time in hospital.


"Non small cell lung cancer and gastric cancer can both be devastating conditions, with gastric cancer affecting approximately 8,200 people in the UK every year and non small cell lung cancer approximately 38,000. We are very pleased to be able to recommend both capecitabine and gefitinib for use on the NHS today."


Notes


About the appraisals


- When a NICE technology appraisal recommends use of a drug or treatment, or other technology, the NHS must provide funding and resources for it within 3 months of the guidance being published. The NHS is not required to fund treatments that are not recommended by NICE.


Capecitabine


- View the capecitabine guidance for further information.


- Although slightly more expensive to buy than fluorouracil, capecitabine is cheaper to give (as it is oral rather than given via an infusion pump). Therefore capecitabine is cost saving compared with fluorouracil


Gefitinib


- View the gefitinib guidance for further information.


- The manufacturer proposed a patient access scheme where the drug is provided at no cost for patients who are treated for up to two months and, for all other patients', gefitinib would be available at a single fixed cost irrespective of the duration of treatment.


- Gefitinib showed longer progression-free survival and similar effects in terms of overall survival compared with the current treatment of pemetrexed used in combination with cisplatin.


- Smoking cigarettes, pipes, or cigars is the most common cause of lung cancer. Other risk factors include:


1. Smoking cigarettes in the past.

2. Being exposed to second-hand smoke.

3. Being treated with radiation therapy to the breast or chest.

4. Being exposed to asbestos, radon, chromium, nickel, arsenic, soot, or tar.

5. Living where there is air pollution.


When smoking is combined with other risk factors, the risk of developing lung cancer is increased.


Source:

NICE


View drug information on Iressa; Xeloda.

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Melissa J. Moore, UMass Med School Researcher, Mentor, Lauded For Doing High-Risk, High-Impact Research

The American Society for Biochemistry and Molecular Biology has named Melissa J. Moore, a professor at the University of Massachusetts Medical School, the winner of the society's 2011 William C. Rose Award. Moore will present her award lecture, titled "Pre-mRNA Processing and mRNA Metabolism," at 8:30 a.m. April 12 in Ballroom C of the Walter E. Washington Convention Center in Washington, D.C., as part of the Experimental Biology 2011 conference.



Moore, a Howard Hughes Medical Institute investigator, is noted for her work with gene splicing and messenger RNA. She was nominated for the award in recognition of her outstanding contributions to biochemical and molecular biological research and her demonstrated commitment to the training of younger scientists.



"Melissa Moore is a paradigm for the Rose Award," said UMMS professor and chairman C. Robert Matthews in nominating Moore. "She is an outstanding scientist, a caring mentor and a terrific colleague. When she perceives a need - from her students, her colleagues or her institution - she always steps forward to fill that need."



Moore, who arrived at UMMS only a few years ago and today is a co-director of its RNA Therapeutics Institute, has initiated and led several programs there that will affect the development of translational research, Matthews said.



Intrigued by enzymes while working on her undergraduate thesis at the College of William and Mary, the Virginia native applied to only one school for graduate studies - the Massachusetts Institute of Technology - and went on to earn her doctorate in biological chemistry and complete postdoctoral research there. Under the supervision of Nobel laureate Phillip A. Sharp, she focused on RNA metabolism and developed a widely adopted technique for manipulating RNA molecules. Soon thereafter, she joined Brandeis University as a faculty member.



"Melissa's success in mentoring is derived from her uncanny ability to enthusiastically promote cutting-edge science while providing an invigorating and supportive setting for that work," said Melissa Jurica of the University of California, Santa Cruz. "She understands that successful science is carried out by secure and confident people. When I visited her lab as a postdoctoral candidate, everyone in her group underscored her people-managing skills while proclaiming her brilliance."



James E. Dahlberg of the University of Wisconsin-Madison School of Medicine and Public Health said one of Moore's strengths is "her willingness to take provocative and controversial stands on scientific issues, which then serve as a basis for designing clever tests that can either support or rule out her models."



Dahlberg said he appreciated Moore's ability to acknowledge and respond when change is needed: "Often she is right, but on those occasions when she learns that her proposals are incomplete or incorrect, she gladly accepts the facts and does not stubbornly hold to the old ideas just for their own sake."



The William C. Rose Award was established to honor the legacy of Rose, an authority on protein nutrition and former president of the ASBMB. The award consists of a plaque, a $3,000 prize and travel expenses to present a lecture at the ASBMB annual meeting in April in Washington, D.C.



Source:

Angela Hopp

American Society for Biochemistry and Molecular Biology

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DOE JGI Releases IMG 2.0 With All Genomes Refreshed From RefSeq

Version 2.0 of the Integrated Microbial Genomes (IMG) data management system of the U.S. Department of Energy Joint Genome Institute (DOE JGI) has been released to the public. The content of IMG 2.0 has been entirely refreshed and extended with the latest versions of genomes available from the National Center for Biotechnology Information's (NCBI) Reference Sequence collection (RefSeq).



IMG 2.0 features the following enhancements:



*
1541 new public microbial, viral and eukaryotic genomes were added to IMG 2.0, bringing the total to 2301 genomes (595 bacterial, 32archaeal, 13 eukaryotic genomes, and 1661 viruses) of which 2058 are finished and 243 are draft.



*
79 finished and 98 draft genomes sequenced by DOE JGI, bringing this total to 177 microbial genomes generated in-house.



IMG 2.0 extensions include gene-based links to NCBI's Entrez Gene, and other microbial genome systems, such as Lawrence Berkeley National Laboratory's MicrobesOnline and Argonne National Laboratory's PUMA.



IMG, accessible to the public at img.jgi.doe/, is the result of a collaboration between the DOE JGI and Lawrence Berkeley National Laboratory Biological Data Management and Technology Center (BDMTC). IMG is updated on a quarterly basis with new public and JGI genomes. The next update is scheduled for March 1, 2007.







The DOE Joint Genome Institute, supported by the DOE Office of Science, unites the expertise of five national laboratories, Lawrence Berkeley, Lawrence Livermore, Los Alamos, Oak Ridge, and Pacific Northwest, along with the Stanford Human Genome Center to advance genomics in support of the DOE mission related to clean energy generation and environmental characterization and clean-up. DOE JGI's Walnut Creek, Calif. Production Genomics Facility provides integrated high-throughput sequencing and computational analysis that enable systems-based scientific approaches to these challenges. Additional information about DOE JGI can be found at: jgi.doe/.



Contact: David Gilbert


DOE/Joint Genome Institute


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Professor Suzanne Cory Awarded 2009 Pearl Meister Greengard Prize

Professor Suzanne Cory, the former director of the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, has been named the recipient of the 2009 Pearl Meister Greengard Prize.



Professor Cory will receive her prize, created to recognise the accomplishments of outstanding female scientists, at The Rockefeller University in the US on 5 November.



The prize was founded by Rockefeller Nobel laureate Paul Greengard and his wife Ursula von Rydingsvard in honor of Professor Greengard's mother, Pearl Meister Greengard, who died giving birth to him. It has been awarded annually since 2004.



Previous recipients of the prize include 2009 Nobel Prize winners Professor Elizabeth Blackburn and Professor Carol Greider for their work on the enzyme telomerase; and developmental biologist Professor Nicole Marthe Le Douarin, who is renowned for her studies of chimeras.



The 2009 Pearl Meister Greengard Prize was awarded to Professor Cory for her work in cancer and immunogenetics.



Professor Cory has had a career-long scientific partnership with her husband Professor Jerry Adams. In the 1970s, they pioneered recombinant DNA technology in Australia, in order to investigate how immunoglobulin genes encode the antibodies needed to fight infectious agents.



In the 1980s, Professors Cory and Adams switched their attention to the genetic errors that provoke lymphomas and leukaemias. They discovered that the chromosome translocation associated with Burkitt's lymphomas activates an oncogene known as myc, which promotes cell proliferation. With colleagues David Vaux and Andreas Strasser, they later made the surprising discovery that bcl-2, the oncogene activated by chromosome translocation in human follicular lymphoma, stops cells from dying. Their research remains focused on the pathways that control cell death.



Professor Cory said it was a great honour to receive the Pearl Meister Greengard Prize. "I am thrilled be awarded this prize and to be acknowledged alongside women such as Elizabeth Blackburn, Carol Greider and Nicole Le Douarin, for whom I have enormous professional and personal respect," Professor Cory said.



"So many women have made vital contributions to the advancement of scientific knowledge but too often in the past, as in other fields, they have been under-recognised. To have awards such as the Pearl Meister Greengard Prize to recognise their achievements is of enormous significance and provides great encouragement to women to take up a career in science."



Professor Cory was director of the Walter and Eliza Hall Institute for 13 years from 1996 and has recently returned to running a research laboratory in the institute's Molecular Genetics of Cancer Division.



Source:
Penny Fannin


Walter and Eliza Hall Institute

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Cialis Shows Steady Growth in First Nine Months On the US ED Treatment Market

Cialis®(tadalafil) has steadily increased its market share and gained against Viagra® (sildenafil citrate) in the nine months since it was introduced in the U.S. to treat erectile dysfunction (ED). Recent surveys reinforce that the main reason for this growth is because Cialis works for up to 36 hours, allowing a man and his partner time to relax, not worry about planning and be intimate when they want to be.2


For the week ended August 6, weekly new prescription data show Cialis has 20.1 percent of new oral ED treatment prescriptions in the U.S., compared to 14.1 percent for Levitra® (vardenafil HCl) and 65.8 percent for Viagra.3 In total oral ED prescriptions, Cialis has 15.7 percent in the U.S., compared to 11.3 percent for Levitra and 73 percent for Viagra. Cialis has increased its share of total prescriptions every month since its introduction in the U.S.4


According to the findings from two recent surveys, one with men who are being treated with Cialis and the other with physicians who prescribe the product, which were sponsored by Lilly ICOS and conducted by Harris Interactive®:


Patient Survey (300 patients taking Cialis)


Of men in the survey who indicated they preferred Cialis and had used other oral ED treatments, 81 percent stated they preferred Cialis specifically because it works for up to 36 hours.


In the survey, 77 percent of the men surveyed either agreed or strongly agreed with the statement, "with Cialis, I don't have to worry about being intimate within a certain period of time."



Physician Survey (202 primary care physicians (PCPs) and 208 urologists who prescribe Cialis)


The top (81 percent) reason physicians surveyed indicated they recommended Cialis to their patients who have not tried other oral ED treatments was that it works up to 36 hours.


An average of 90 percent of doctors surveyed agreed or strongly agreed with the statement, "I prescribe Cialis to men with ED who desire greater freedom from planning" (92 percent of 202 primary care physicians and 89 percent of 208 urologists).


An average of 97 percent of physicians surveyed believe that their patients are "satisfied" to "extremely satisfied" with Cialis (96 percent of primary care physicians and 98 percent of urologists).



"These results support what we are already seeing in markets around the world," said Leonard Blum, vice president of marketing, ICOS Corporation. "Men and their doctors who are choosing Cialis as their ED treatment are doing so because of the distinctive attributes it offers patients."















In addition to working up to 36 hours in most men, Cialis can be taken on an empty stomach or with a meal, without concern that high-fat food will reduce the absorption of the medicine. These benefits allow a man and his partner to relax and let intimacy happen when the moment is right for them.


About the Surveys


The two surveys, sponsored by Lilly ICOS LLC, were conducted online by Harris Interactive® between June 3 and June 9, 2004. PCPs (202) and Urologists (208) who were all current Cialis prescribers were recruited from the Harris Interactive Physicians Panel via an email invitation, which outlined the purpose of the survey in general terms. Physicians were given an honorarium in exchange for their participation.


The patient sample was recruited from the Harris Interactive Chronic Illness and general panels. To qualify for this survey, patient respondents had to meet the criteria of being male between the ages of 40 and 70 years, be a U.S. resident, have erectile dysfunction and be taking Cialis.


Data from the physicians' sample were unweighted and data from the patients' sample were weighted for age, sex, race/ethnicity, education, income, religion and propensity to be online to align them with population proportions. In theory, with probability samples of this size, one could say with 90 percent certainty that the results have a sampling error of plus or minus seven percentage points of what they would be if the entire U.S. online population of PCPs and urologists who currently prescribe Cialis to patients OR the total U.S. population of men who currently take Cialis for ED had been surveyed with complete accuracy. These online samples were not probability samples.


About Cialis


Cialis, approved by the FDA in November 2003 for the treatment of erectile dysfunction, is the only oral ED treatment shown to improve erectile function up to 36 hours in most men. Cialis can be taken without regard to food. The absorption of Cialis is not reduced by food, including high-fat foods. Cialis is currently available in approximately 90 countries, including Australia, Brazil, Mexico, Canada, the United States and countries throughout Europe. Nearly three million patients worldwide have been treated with Cialis since its first introduction in February 2003.


Cialis is available by prescription only and is not for everyone. Men taking nitrates, often used for chest pain, or certain alpha-blockers for prostate problems or high blood pressure, should not take Cialis. Such combinations could cause a sudden, unsafe drop in blood pressure.


Men should discuss their health status with their doctors to ensure Cialis is right for them and that they are healthy enough for sexual activity.


The most common side effects with Cialis were headache, upset stomach, delayed backache and muscle ache. Although rare, men who experience an erection for more than four hours should seek immediate medical attention. Men should not drink alcohol in excess with Cialis. Cialis studies were not designed to assess multiple intercourse attempts after a single dose.


For full patient information, visit cialis.


About ED


ED is defined as the consistent inability to attain and maintain an erection sufficient for sexual intercourse. ED affects an estimated 152 million men and their partners worldwide.5 Experts believe that 80 - 90 percent of ED cases are related to a physical or medical condition, like diabetes, cardiovascular diseases, and prostate cancer treatment, while 10 - 20 percent are due to psychological causes.6,7 In many cases, however, both psychological and physical factors contribute to the condition.8


About Lilly ICOS LLC


Lilly ICOS LLC, a joint venture between ICOS Corporation (Nasdaq: ICOS) and Eli Lilly and Company (NYSE: LLY), developed tadalafil for the treatment of erectile dysfunction.


Lilly, a leading innovation-driven corporation is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations.

Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs. Additional information about Lilly is available at lilly.


ICOS Corporation, a biotechnology company, is dedicated to bringing innovative therapeutics to patients. Headquartered in Bothell, Washington, ICOS is marketing its first product, Cialis® (tadalafil), for the treatment of erectile dysfunction. ICOS is working to develop treatments for serious unmet medical conditions such as chronic obstructive pulmonary disease, benign prostatic hyperplasia, cancer and inflammatory diseases.


Except for historical information contained herein, this press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements are based on current expectations, estimates and projections about the industry, management beliefs and certain assumptions made by the management of ICOS and Lilly. Investors are cautioned that matters subject to forward-looking statements involve risks and uncertainties, including economic, competitive, governmental, technological, legal and other factors discussed in the two companies' respective filings with the Securities and Exchange Commission, which may affect the business and prospects of the two companies and Lilly ICOS. Results and the timing and outcome of events may differ materially from those expressed or implied by the forward-looking statements in this press release. More specifically, there can be no assurance that Cialis will achieve commercial success or that competing products will not pre-empt market opportunities that might exist for the product.


1. Cialis® is a registered trademark of Lilly ICOS LLC. All other trademarks are the property of their respective owners.

2. Individual results may vary. Not studied for multiple attempts per dose.

3. IMS National Prescription Audit Plus7 ™ August 2004.

4. IMS National Prescription Audit Plus™ June 2004

5. Aytac Ia, McKinlay JB, Krane RJ. The Likely Worldwide Increase in Erectile Dysfunction Between 1995 and 2025 and Some Possible Policy Consequences. BJU Int 1999; 84: 50-56.

6. Shabsigh, R. (2002). Back To Great Sex: Overcome ED and Reclaim Lost Intimacy . New York: Kensington.

7. Diseases and Conditions: Impotence, impotence/FAQ/index.asp. Data accessed 11.20.03

8. Lue, Tom F. Erectile Dysfunction. N Engl J Med 2000; 342: 1802-1813


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