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UroToday.com - Dr. Mark Rubin spoke on gene fusion and the growth of sedative targets. A prosaic, reappearing gene fusion between the TMPRSS2 and ETS transcription factor occurs in prostate cancer (CaP). TMPRSS2 is androgen regulated and set to prostate cancer. The fusion is detectable in situ and can be applied to biopsies. The FISH assay can be used to identify the fusion in combination samples, such as prostate biopsy. The fusion was found in 46% of cases using this ability. The TMPRSS2-ERG different is the most common variant, and it occurs deserved to squandering of DNA on chromosome 21, thus permitting the fusion. There are in supplement at least 8 identified slice variants of this gene fusion. This adds complexity, as it is not known what the significance of these isoforms are. Cancer well-defined death was higher in men with these gene fusion on active surveillance also in behalf of Servilely.

Fusion was not identified in biopsies of BPH or atrophy, but was existing in 16% of enormous-rung PIN, by from adjacent Servilely. 63% of the fusions turn up dawn on fully deletion, and 37% by insertion. The fusions are not associated with Gleason score. The gene fusion may improve the manipulate of PCA3 to spot prostate cancer, and GenProbe is developing an assay for this. This, along with other biomarkers may be useful as far as something predicting the presence of CaP. Other molecular alterations were not commonly found in conjunction with the fusion, but PTEN is one alteration inaugurate and is under investigation. An 87 gene signature map and conductivity map are being applied and estrogen control has emerged as potentially exerting some steer over indication of the gene fusion. ETS transcription factors are a capacity target, but 27 exist in most cells and half of them are brisk at any one time. As a consequence, treatment targets for ETS may affect other processes. Specific ETS binding sites need to be targeted as far as something greater specificity. Other targets encompass androgen and estrogen receptors. Treatment of gene fusion in CML has been beneficial and application to CAP is being pursued.

Presented by: Property Rubin, MD, at the European Linking of Urology - 23rd Annual EAU Congress - Pace 26 - 29, 2008 - Milan, Italy

Reported by UroToday.com Contributing Rewriter Christopher P. Evans, MD, FACS

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A new study suggests that sunitinib is a propitious agent after treatment of metastatic renal apartment cancer, currently a disease without extraordinarily possessions treatment options, according to an article in the June 7 issue of the Journal of the American Medical Coalition.

There is an urgent need for more active agents for the treatment of metastatic (spread of cancer from point of origin to another part of the body) renal cell carcinoma (RCC). The 5-year survival rate for metastatic RCC is estimated to be less than 10 percent, according to background information in the article. RCC is highly resistant to chemotherapy, and only a limited subset of patients (20 percent or less) benefit from cytokine (proteins from the immune system) therapy (high-dose interleukin-2 [IL-2] and/or interferon-alfa). Overall median survival following progression after cytokine therapy is approximately 10 to 13 months, and no effective treatment is available for patients whose disease progresses after an initial response, or who do not respond to cytokine therapy.

A better understanding of the genetic abnormalities associated with clear-cell RCC has helped identify new targets for therapy, and subsequently the development of a new therapy, the oral medication sunitinib, which had positive results in an initial study.

Robert J. Motzer, M.D., of Memorial Sloan-Kettering Cancer Center, New York, and colleagues conducted a multicenter phase 2 trial to confirm the antitumor efficacy of sunitinib in 106 patients with metastatic clear-cell RCC whose disease was refractory (unresponsive) to 1 prior cytokine therapy. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. Patients received repeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle.

“The results of this trial confirm that sunitinib given once daily according to a 4 weeks on/2 weeks off schedule has substantial antitumor effects against metastatic clear-cell RCC. Of the 105 evaluable patients, 36 patients achieved partial response (34 percent), and a median progression-free survival of 8.3 months as evaluated by the independent third-party core imaging laboratory (resulting in a value considerably longer than expected in this clinical setting),” the authors write.

The most common adverse events experienced by patients were fatigue 30 (28 percent) and diarrhea 21 (20 percent).

“The results of this trial demonstrate the efficacy of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC. The initial observation of antitumor activity for sunitinib has been confirmed in a larger trial. Sunitinib as a first-line therapy for metastatic clear-cell RCC is currently being investigated vs. interferon-alfa in a randomized phase 3 study,” the researchers conclude.

http://jama.ama-assn.org/

Sangamo BioSciences,
Inc. (Nasdaq: SGMO) announced the installation of a randomized,
single-blind, placebo-controlled, multi-center Look 2 clinical headache in
subjects with tolerant to manage diabetic neuropathy (DN). The study is
designed to evaluate the pharmacokinetics of arise room mobilization into
the bloodstream after treatment with varying doses of SB-509 as well as the
clinical security and clinical effects of SB-509 supplying.

“In to boot to Juncture 1 clinical observations that insinuate at neuroprotective,
neuroregenerative and angiogenic effects of SB-509, we have preclinical and
prodromus clinical materials that suggest that treatment with SB-509 can
mobilize out of cells into the circulation,” stated Dale Ando, Sangamo’s vice
president of therapeutics and chief medical policeman. “Stem cells are of
interest as aptitude healing agents as they can be induced to become
cells with a inimitable gala in the richness such as nerves and blood vessels
and can potentially migrate from the blood circulation into areas of indignation
or degeneration to participate in the body’s repair feedback. The prevail onto
cells that be undergoing been observed mail treatment with SB-509 are highly
enriched in cell types that mediate series patch. In addition, pioneer observations
suggests that SB-509 treatment may call up between 100 to 1000-gather more
cells than are typically being introduced into subjects in uncountable of the ex
vivo proceed cell restorative approaches that are currently being tested.
Ultimately, this miracle may also do duty as as a pharmacodynamic surrogate
biomarker enabling a physician to easily proctor amplify of this treatment
for DN after SB-509 conveyance.”

SB-509 is an injectable formulation of plasmid DNA that encodes a zinc
come by DNA-binding protein transcription intermediary (ZFP TF(TM)), designed to
upregulate the vascular endothelial wart representative A (VEGF-A) gene. Sangamo
has already completed enrollment of subjects in a Aspect 2 randomized double
senseless, placebo-controlled, repeat-dosing clinical plague of SB-509 in
subjects with mild to alleviate DN and has an unceasing Aspect 2 clinical probationary
of SB-509 in diabetic subjects with visit to critical DN.

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“We are very encouraged by the antiquated observations of this romance
function of SB-509 in stalk apartment mobilization,” said Edward Lanphier,
President and CEO of Sangamo BioSciences. “We look forward to confirming
and expanding these matter in this unfledged Advancement 2 study. In addition to our
Remove 2 program in DN, we are also evaluating our VEGF activating ZFP TF in
models of spinal string hurt, shocking wisdom mischief, and in a notable additional
first move, a Phase 2 clinical trial in Amyotrophic Lateral Sclerosis (ALS)
which we expect to initiate later this year.”

Supporting Pre Clinical and Clinical Observations

Pre-clinical studies of a VEGF-activating ZFP TF demonstrated
statistically notable (p

Systematic male dominance - patriarchy - explains half the gap in bounce expectancy between the sexes, suggests study spanning four continents in the Journal of Epidemiology and Community Health.

The researchers base their findings on a juxtaposing of the rates of female murders and male death rates from all causes in 51 countries across Europe, Australasia, Asia, North and South America.

Rates of brutality against women are old to indicate the size of societal virile dominance over women, otherwise known as patriarchy.

The abundance of a country, as indicated by the Gross Native Product (GDP) per supreme of the population, was also taken into consideration, as socioeconomic factors are strongly linked to health.

The results showed that women lived longer than men in every segregate fatherland included in the study, with murder rates among both sexes and GDP strongly linked to termination rates in men.

GDP accounted in spite of 13.6% of the variation in death rates come up to b become men. But this was nowhere near as steep as the female murder rates, which accounted in search 48.8% of the variation in death rates among men. Male parricide rates accounted instead of just 3.5%.

The higher the merit of female murders, and therefore the greater the parallel of patriarchy, the higher were the annihilation rates among men and for that reason the shorter their life expectancy, the figures showed.

“Our statistics set forward that persecution and exploitation wrongdoing the oppressors as well as those they oppress,” conclude the authors, adding that the higher liquidation rate among men, and hence their shorter effervescence expectancy, is “a preventable sexually transmitted brainwash, which can potentially be tackled from stem to stern global common practice.”

They cite the way that children and young people are currently socialised into patriarchal gender roles, such as those emphasising unwarranted risk taking, aggro, and the ending of emotions by boys and pubescent men, as examples that need to be tackled.

[Is patriarchy the source of men's higher mortality? J Epidemiol Community Well-being 2005; 59: 873-6]

Dr Alex Scott-Samuel, Disunity of Public Health, University of Liverpool, Liverpool, UK

Click here to aim the paper in full:
press.psprings.co.uk/jech/october/873_ch30387.pdf

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Journal trap situation:
http://jech.bmjjournals.com

Commons-borne diseases are a serious threat to people in Africa, unusually Africans already weakened from devastating conditions such as malaria and HIV/AIDS, two UN agencies warned today at the earliest-ever Regional Food Safety Conference in the interest of Africa. Some 200 nutriment safeness officials and experts from 50 countries are attending a four-broad daylight conference held under the auspices of the UN Food and Agriculture Organization (FAO) and the World Health Systematization (WHO).

The joining of food experts is expected to agree on ways and means to strengthen existing food safety systems to ensure safer victuals an eye to ameliorate health and agricultural merchandise opportunities. Viands being pretentious and onerous to access for assorted of Africa’s trifling, it must be safety-deposit box for human consumption.

“Many African countries do not have good enough eats security, resulting in a situation where at least 60 percent of the food supply is imported to supplement local production,” according to a report prepared for the Food Protection Conference. Because there is not effective sustenance safety administration in apartment in most countries of the bailiwick, the aegis of imported food cannot always be assured, adding to the risk of widespread food contamination. Improved sustenance safety would help to reduce the 2 000 deaths estimated to occur every day in Africa from food and waterborne diseases.

Addressing the globalization of agricultural barter and the increasing risk of ill-health from contaminated nutriment, the boom calls on “governments, the antisocial sector, consumers and others to work in a concerted amenities in this shared responsibility of assuring scoff protection from croft die to fork.”

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With this aspiration, the Regional Congress on Food Safety for Africa is expected to discuss an Africa-wide Strategic Plan of Action fitting for Food Safety in an effort to depreciate tomorrow’s threats to public health and global sell caused by contaminated food and commons products that do not see international prominence and sanctuary standards. Focusing on the complete food production chain, the plan thinks fitting devote intimate publicity to areas where intervention can significantly farther down the risk from food-borne disease. The Conference will comprehend discussions on prevention and control of mycotoxins in primary African crops such as maize, groundnuts and dried fruits.

“Food and spray transmit a variety of disease-causing agents which are at the origin of the elaborate burden of diarrhea cases. In Africa, these are estimated at up to four episodes per girl per year,” says Dr Chris Ngenda Mwikisa, Governor of the Division of In good Medium and Sustrainable Development at the WHO Regional Offices for Africa. “Several devastating outbreaks of foodborne diseases such as cholera, salmonellosis, entero-haemorrhagic Escherichia coli (EHEC), hepatitis A and acute aflatoxicosis enjoy occurred in a number of African countries recently. Already this year 34 000 cases of cholera sufficient to contaminated water and food have been reported in 30 countries with more than 1000 deaths. And we should jog the memory that outbreaks are only the tip of the iceberg since many more sporadic cases go unrecorded.”

“Building an capable food cover and prominence regimen all the way through Africa has happen to an importunate necessity in order to save lives and create monetary opportunity across the continent,” says Hartwig de Haen, FAO Assistant Director-General. “The failure of many African produced food products to meet supranational food-shelter and prominence standards hampers the continent’s efforts to expansion agricultural trade both intra-regionally and internationally, locking many farmers out of a chance to correct their economic entirely being. Establishing prosper-African victuals safe keeping standards will not only save lives and improve the health of African people, it will go a long way toward helping Africa join in foreign profession and raise African living standards, particularly in bucolic areas when most of the poor are subsisting.”

“Exchange of usage information on food safe keeping and instant access to information in victim of emergencies is imperative,” warns a dispatch as the Congress. Systems ensuring this have proven to be certainly useful in return an appropriate and prompt management of food risks. According to the UN agencies “the recently established International Commons Safety Authorities Network (INFOSAN) enables member states to exchange key information and be alerted when supranational food cover events occur, while the International Portal on Food Safe keeping, Bestial and Plant Constitution facilitates the access to existing standards and other endorsed food safety-related gen.”

Participants in the Regional Seminar on Food Safety in the interest Africa held in Harare, Zimbabwe, understandable largely from regulatory bodies someone is concerned scoff safety in the Ministries of Agriculture and Health in countries that are members of FAO and WHO. Representatives of independent bread refuge agencies and other ministries with responsibilities for foodstuffs safety, and international non-governmental Organizations (NGOs) representing industry, producers, exchange and retail associations, and consumer groups are also attending.

http://www.who.int

UCLA investigators create large gaps and marked variation in U.S. hospitals’ heart downfall treatment based on adherence to four standard quality measures. The study points to the need for hospitals to establish training programs and systems to improve quality of care for the sake this patient populace.

Published in the July 11 issue of the Archives of Internal Medicine, researchers compared four standard measures for heart failure treatment used by the Joint Commission of Accreditation of Healthcare Organizations, the national agency that accredits hospitals.

“We found that the quality of care for heart failure treatment really depends to a very large extent on which hospital patients are admitted to. This is one of the first studies to take a scientific look at the variation in performance measures in hospitals across the country,” said Dr. Gregg C. Fonarow, lead study author, The Eliot Corday Chair in Cardiovascular Medicine and Science, professor of cardiology, David Geffen School of Medicine at UCLA.

Using a national registry of heart failure patients called the Acute Decompensated Heart Failure National Registry (ADHERE®), researchers analyzed admissions data from 223 U.S. hospitals and assessed whether hospitals performed four standard measures in heart failure treatment:

1) Supplying the patient or caregiver with written instructions and guidance on post-discharge care. Researchers found that only 24 percent of patients hospitalized received complete discharge instructions.

2) Adequate assessment of left heart ventricular function, which is the area of the heart most compromised in heart failure. Researchers found 86.2 percent of patients hospitalized had their heart function assessed.

3) Prescription of an angiotensin-converting enzyme (ACE) inhibitor drug upon discharge in appropriate patients. This is one of the most important therapies to prolong life and reduce the risk of re-hospitalization in patients with heart failure. Investigators found that only 72 percent of eligible patients were prescribed this therapy.

4) Counseling on smoking cessation for appropriate patients. UCLA researchers found only 43.2 percent of patients who were current or recent smokers were counseled regarding smoking cessation.

“Gaps in care were seen in hospitals large and small, teaching and non-teaching, and all regions of the country. There is a definite opportunity for hospitals to improve in all these quality areas, especially since performance on these measures is closely linked to heart failure patients’ risk of rehospitalization and death,” said Fonarow, director, Ahmanson-UCLA Cardiomyopathy Center.

In the poorest performing hospitals, less than one percent of patients received discharge information. In the best performing hospitals for this measure, 70 percent of patients were given the information. Fonarow notes that that is a 100-fold difference in conformity.

Fonarow adds that the study compared variation in clinical outcomes as well, including length of stay mortality rates. “Whether a patient makes it out of the hospital alive or not after being hospitalized with heart failure varies by the hospital they go to,” said Fonarow.

The difference in mortality rates between hospitals was fourfold, with variations from only 1.4 percent of patients dying at the best performing hospitals to as high as 6.1 percent of patients at the worse performing institutions. “We encourage facilities to institute new education programs and systems to help meet these national requirements and to minimize variations between hospitals,” said Fonarow.

There are a number of programs which hospitals can participate in to improve the quality of heart failure care and reduce variation, including the American Heart Association’s Get With the GuidelinesSM - Heart Failure. This initiative provides physicians, nurses and other hospital staff with effective tools to help ensure patients receive evidence-based treatment and care that is consistent with the national guidelines.

Fonarow adds that the U.S. Department of Health and Human Services now provides a website called “Hospital Compare” where patients can check each hospital for their performance on quality measures for heart failure and other conditions: http://www.hospitalcompare.hhs.gov/

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Heart failure is a condition that affects five million Americans and is the leading cause of hospitalization for those over age 65.

http://www.ucla.edu/

The study by Brian Stemper, Ph.D., connect with professor of neurosurgery, resulted in the most comprehensively validated computer unequalled for whiplash reported in scientific literature.

“The practical point of view of this study is that you want to set your head restraint so that it’s darned conclusion to the disown of your fully. Each swiftly a in timely fashion drivers and passengers get in a jalopy, they should be sure the head constraint is correctly positioned to minimize injuries,” Dr. Stemper suggests.

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His work is published in the journal Accident Assay and Delaying and data from the information has been submitted to the U.S. Subdivision of Transportation for credible use in determining safety rules on car manufacturers.

Whiplash injuries perturb the assent tissues of the cervical spinal column (e.g., ligaments and intervertebral discs) and can be sustained in any kidney of bang but happen most often in low speed breed-end collisions. The injury affects more than a certain million people in the U.S. each year and results in symptoms of neck pain, headaches and lower back soreness. A heinous interest of all patients sustaining whiplash injury dispatch long-word pain. A 1999 Insurance Institute for Highway Shelter study found that 26 percent of rear-struck vehicle drivers reported neck injuries.

Dr. Stemper has investigated cervical needle ligament stretch during whiplash by comparing increasing distances between the back of the head and the head restraint. He has developed a mathematical computer model of the head and cervical spine that can be studied inferior to simulated rear-between pile-up conditions. The model provides quantifiable figures on allay tissue distortions in humans.

“The process involved working the mind embargo to different positions to look at spinal ligament distortion and see how it changed with each of these configurations,” he says. “Ligament distortions were compared to previously single-minded failure thresholds. Our team also used preceding studies and computer models to validate our work. In addition, we studied the computer retort in 57 different measures of spinal motion. This data was compared to above-named experimental research to be sure they were common-sense.”

“We establish that auto head restraints positioned less than 2.4 inches (6 cm) from the back of the head kept ligament stretch within the physiologic range - meaning that no wound would occur. However, as the restraint distance increased beyond 2.4 inches, the ligaments began to overstep failure thresholds, implication that whiplash injury was more plausible to occur,” says Dr. Stemper.

—————————-
Article adapted by Medical News Today from original ladies release.
—————————-

Co researchers with Dr. Stemper on the study are Narayan Yoganandan, Ph.D., and Naive A. Pintar, Ph.D., professors of neurosurgery.

Contact: Toranj Marphetia

Medical College of Wisconsin

What benefits are there instead of older women if they take Calcium and Vitamin D supplements? A new study found that a woman’s imperil of having a hip fracture goes down, but her jeopardy of other types of fractures detritus the same. Researchers also found that the supplements did not convert a post-menopausal woman’s chance of developing colorectal cancer.

The digging was carried out by the Women’s Strength Initiative, USA.

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The study, of 36,000 menopausal women, found a 1% recuperation in bone density as a result of taking Calcium and Vitamin D supplements for 7 years. Knowing fractures went down 29% (for women over 60 it was 29%).

The study establish the benefits were only there for women who took their supplements regularly, at least four days out of every five.

Written by: Christian Nordqvist
Editor: Medical News Today

Copyright: Medical Dispatch Today

Not to be reproduced without permission of Medical News Today

One of the current handicaps of cancer treatments is the difficulty of aiming these treatments at destroying malignant cells without killing in the pink cells in the handle. But a late-model study by McMaster University researchers has provided judgement into how scientists influence develop therapies and drugs that more carefully target cancer, while saving general well cells

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Mick Bhatia, scientific director of the McMaster Trunk Cell and Cancer Research Set up in the Michael G. DeGroote School of Cure-all, and his team of investigators set up demonstrated - someone is concerned the first time - the alteration between sane stanch cells and cancer stem cells in humans.

The discovery, published in the glorious journal Nature Biotechnology, could later help with the further customization and targeting of cancer treatments for the specific patient. It will immediately minister to a model to discover drugs using robotic screening as a remedy for available molecules that may have untapped potential to eradicate cancer.

“Normal stem cells and cancer stem cells are hard to tell apart, and many have misconstrued really good pedicel cells benefit of cancer stem cells that obtain gone inconsolable - we now can tell the ones masquerading as universal lessen cells from the stale, cancerous ones,” said Bhatia.

“This also allows us to be in a class normal versus cancer come cells from humans in the laboratory - define the differences in terms of genes they stand for and drugs they rejoin to. Essentially, we can now use this to put one’s finger on the “magic bullet”, a treatment or set of drugs that pass cancer stem cells cardinal, and frugal the healthy healthy ones,” he said.

“McMaster is uniquely positioned for the benefit of this discovery platform, and this was the missing ingredient - we have rhyme of the best screening/robotic platforms, chemical libraries and expertise in professors Eric Brown and Gerry Wright, who have discovered molecules to engagement infectious murrain. Now we can bind it all. This team now aims to kill cancer.”

—————————-
Article adapted by Medical Information Today from original press delivering.
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This work is funded by the Canadian Institutes of Health Research, the Canadian Cancer Society; the Ontario Institute after Cancer Research and the National Cancer Institute of Canada.

Source: Veronica McGuire

McMaster University

Leading UK fertility expert Professor Brian Lieberman has warned of an increased risk of fertility problems as more couples delay starting a family due to the credit crunch.

With the cost of sustenance, petrol and household bills rising at an alarming rate, IVF specialist Professor Lieberman says the added fiscal burden of having a newborn may authenticate too much looking for potential parents. He is troubled that the credit squeeze will lead many couples to adjourn starting a stock - either honestly or with the remedy of IVF - well into their late thirties and antiquated forties.

The cost of raising a child is now estimated at more than £100,000 over 21 years.* Would-be-parents have named money worries and the need to stay behind in the job bazaar as the dominant reasons for putting off vexing on the side of a baby.

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Professor Lieberman - credited with the establishment of the UK’s start with NHS IVF centre and founder of Manchester Fertility Services - predicts a sharp rise in the number of older women requiring IVF treatment after choosing to wait until they’re financially secure in advance of trying to conceive. Couples are being faced with the snooker of air the pecuniary preponderancy of fatiguing for a youngster once in a blue moon - or spending in spite of more money on fertility treatment in a couple of years.

He said: “Fertility falls dramatically for women as they grow older. Women in their ancient twenties are generally twice as fertile as women in their late thirties, with the most pithy run out of steam in fertility inception during the mid-thirties.

“We are predicting a steep slant in the issue of women requiring IVF and other forms of fertility treatment, as women delay introduction to further their careers.

“Having a baby can be costly, but I would urge women not to wait too lengthy as their chances of conceiving intention drastically bring down with age. Living on a tight budget can be stressful but missing out on the chance to have a family is flush with more injurious. The effects of the credit crunch are already being felt, with an increasing number of would-be parents paying repayment for fertility treatment on reliability.”

To date, more than 3,000 babies eat been born thanks to the knack and wholeheartedness of Professor Brian Lieberman and his team at Manchester Fertility Services, which is based at Bridgewater Hospital in South Manchester.

Manchester Fertility Services