Range Of Rett Syndrome Revealed By Genetic Analysis
The first comprehensive analysis of the clinical effects of genetic mutations involved in Rett syndrome will enable affected families to receive a in addition accurate indication of their child’s prognosis.
The research was undertaken by an international collaboration based on information granted by the agency of families and clinicians from around the nature to the InterRett online database at the Telethon Institute for Child Health Research.
The results have honest been published in the March number printed at once of the prestigious international magazine Neurology.
Report co-author, Dr Helen Leonard, who heads the Australian Rett Syndrome Study, said the findings have revealed a wide variability in the effects of the syndrome.
“This is the first time that we’ve had quality information about a sufficient number of cases to be able to do a rigorous analysis comparing specific genetic mutations with they way the disorder is manifested in affected girls,” Dr Leonard said.
“While Rett syndrome is caused through a mutation upon the body the MECP2 gene on the X chromosome, variations in the mutation determine the severity of symptoms.
“Our resolution of eight common mutations that account for two-thirds of cases, showed considerable variation in abilities”
Dr Leonard said the information would be of great value to families, clinicians and carers.
“Many parents have found the lack of knowledge about their daughter’s prognosis very distressing and will welcome a clearer indication of what they might expect in the future,” Dr Leonard said.
“Our findings in truth emphasised how much variability there is in the syndrome and we hope that information will assist with earlier diagnosis.”
Dr Leonard said that girls with the milder form of Rett syndrome may retain some language, hand function and the ability to walk. In contrast, those with the severe form dress in’t show the usual pattern of regression but are affected from birth.
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Article adapted by Medical News Today from original clasp release.
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InterRett is an online database that now contains information on more than 1200 people from around the world. It is fully funded by the International Rett Syndrome Foundation.
not far from Rett Syndrome:
Rett syndrome is a relatively rare but serious neurological disorder that usually affects girls. The clinical diagnosis has often been uncertain in early childhood as the symptoms may be confused with those occurring in other disorders such as autism, cerebral palsy and developmental delay.
Rett syndrome affects around one in every 8,500 female births. Mutations in the MECP2 gene on the X chromosome have been identified as a cause of Rett syndrome. There is no known cure.
Source: Liz Chester
Research Australia
New STD Data Shows Need For Abstinence Education, Says Family Research Council
Moira Gaul, Family Research Council’s Director of Women’s Health declared that the alarming new data released at the CDC’s public convention on sexually transmitted diseases (STDs) shows the botch of so-called “comprehensive” or contraceptive- and condom-based sex education. “Only a risk-avoidance or sexual abstinence-until-marriage strategy will be effective in helping to reverse the current STD prevailing,” said Ms. Gaul.
This week the Centers for Disease Control and Prevention (CDC) released a study indicating that 1 in 4 teen girls, or 3.2 million, are infected by a sexually transmitted infection (STI). In addition, findings from brace other studies presented show that of the youthful women receiving contraceptive services, over half are not receiving congruous screening and treatment for STIs.
“Taken altogether these findings represent confirmation of a simmering STD epidemic and tremendous negligence in care for those most at risk for contracting STDs,” noted Gaul. “The call for an effective public health prevention strategy could not have existence more urgent.”
“While abundant of the medical and public soundness community pays edge service to prevention with respect to our young people, these results continue to provide sad evidence that the focus is on facilitating high-risk behavior rather than true primary and even secondary prevention,” Gaul declared. “Abstinence education offers an effective and holistic approach to protect our young people’s current and future health by teaching them necessary skills to build healthy relationships and providing accurate medical information concerning risks of sexual behavior.”
FRC also called upon policy-making bodies, such as the American Academy of Pediatrics, to develop and formalize clinical counseling interventions directed toward sexual risk avoidance strategies for adolescents. “Such strategies would mirror, and thus strengthen, the risk avoidance prevention messages presented to adolescents regarding tobacco, alcohol, drugs, and violence,” said Gaul. “This peril avoidance message is the most good form of main prevention young men can receive, and it’s time for the medical and public health communities to step up to the plate.”
Family Research Council
http://www.frc.org
The Clinical Management Of Patients With A Small Volume Of Prostatic Cancer On Biopsy: What Are The Risks Of Progression?
UroToday.com - PSA screening has led to the over discovery of small volume and perhaps indolent prostate cancer (CaP). In the online version of Cancer, Dr. Hamden and colleagues report a meta-analysis on whether patients with microfocal CaP on biopsy have adverse pathologic findings or any significant peril of PSA recurrence after undergoing radical prostatectomy (RP).
A total of 238 articles were carefully evaluated and in the definitive review 29 articles addressed the specific question of the correlation between small-volume cancer on biopsy and pathologic findings, biochemical or clinical progression, or mortality. Where possible, outcome data were pooled to estimate the overall risk associated with small-volume cancer at biopsy. A fixed-effect model was used if there was no evidence of heterogeneity at the significance level of P=.1. If heterogeneity was evident, then a random-effects original was used.
All the studies were retrospective. Studies varied in the maximum number of biopsy cores that were allowed to qualify for the definition of microfocal CaP and whether the maximum length of cancer and highest Gleason score were specified. The most common values adopted were a single positive core and a cutoff value of 3mm for the CaP length. Regarding the likelihood that no CaP would be found in the RP specimen, the occurrence rate was 0.8%. The overall estimate of the risk that patients with microfocal CaP would have extracapsular increase (ECE) at RP was 17.6%. The combined estimate for a positive surgical margin among men with microfocal CaP was 12%. The range of PSA recurrences among this population was 0-26%, with an estimated risk of 8.6%. Among watchful staying studies, the number of patients was small, and a rising PSA was reported in 9 of 15 patients who had a microfocus of CaP, and 4% experienced clinical progression. Conversion to definitive therapy occurred in 30%.
The authors acknowledge several limitations to include marked variation in men diagnosed due to an elevated PSA (18.5-95%). Also, the proportion of patients excluded from the final analysis was up to 29%. Finally, no details about surgical expertise were included and may account for different outcomes. Despite these limitations, the overall suggestion is that a feeble volume of CaP in prostatic biopsies is not necessarily indicative of a good prognosis.
Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS Professor & Chairman Department of Urology University of California, Davis, School of Medicine Sacramento, CA
UroToday - the only urology website with original content written by global urology key persuasion leaders actively engaged in clinical usage.
To access the latest urology news releases from UroToday, be on the point to: www.urotoday.com
Copyright &pattern after; 2008 - UroToday
An Important Message To Anyone Taking Viagra… From The Women Who Love You
The new Zantrex®-3 Insta•Shot™ commercial is really funny… further with serious undertones.
“I love the commercial because sometimes my husband remembers to take his viagra but forgets to curb awake long enough for it to make any difference,” says a customer menial duties rep (who wishes to remain anonymous) at Zoller® Labs, the makers of Zantrex-3. “When we first showed the commercial to our employees the men looked embarrassed. Meanwhile the women were nodding their heads in complete agreement. Maybe it’s just my female perspective but verily, what good is a male potency pill if your significant other doesn’t even have the energy to stay awake?”
The commercial for Zantrex-3 Insta•Shot&mechanical employment;, which can now be seen on YouTube (search Zantrex3) depicts an everything too common scene… men too exhausted by of their hectic schedules to have existence interested in anything but sleep. And, of course, there’s the female balking. The commercial’s opening line says it all: “No matter how much Viagra you need… you still need energy to make things ‘happen.’”
There’s no question that over the past five years the Zantrex-3 bolt has become that express the same idea with extreme energy (even though Zantrex-3 diet pills are mould in the weight loss section of virtually each store in America that has a weight loss section). So it was only a matter of opportunity before the clever marketers at Zantrex entered the new, ultra-hip energy shot market. But rather than concentrate on extreme sports (although they have a very cool “free-running” trading and sponsor MMA fable “Dangerous” Dan Henderson), Zantrex-3 Insta•Shot is focusing in continuance the overly-exhausted, over-40 male market with individual of the funniest, if not most interesting, commercials of the year, especially for an energy shot.
“Our tongue-in-cheek approach hides a dangerous message,” explains Gina Daines, spokesperson for Zoller Labs. “Both men and women face grinding schedules with more stress and longer working hours than our parents and grandparents had to face. And unfortunately, perhaps the biggest victim of our fast-paced lifestyle is enhancer. And that’s no joke for millions of couples. If Zantrex-3 Insta•reach can dart in some energy into the bedroom, well that would be a dexterous thing. No, that would be a great thing, wouldn’t it?”
About Zantrex-3 Ultra Potent Insta•Shot
Fully distributed at GNC, Zantrex-3 Insta•Shot will soon be turn to account at 7-11, Wal-Mart, Walgreen’s, CVS and, as they say in the ad, “smarter retailers nationwide.” Insta•Shot’s “Octane Orange” flavor is a real step up from the acrid, bitter taste of most energy drinks and shots. The formula boasts extreme energy that’s “fast-acting, long-lasting” and with “no crash.” But it’s the “Ultra-Potent” message in the commercial that has everyone talking.
http://www.zantrex-3.com
South China Morning Post Examines Efforts To Raise Awareness About HIV/AIDS Among Sex Workers In Bali, Indonesia
The South China Morning Post on Tuesday examined efforts to raise awareness about HIV/AIDS among commercial sex workers in Bali, Indonesia. Official figures show that about 4,000 clan were living with HIV/AIDS in Bali as of August 2007 and that at least 1,000 more command contract the virus this year. In addition, more than half of the new cases will be transmitted through sexual contact, according to the Kerti Praja Foundation, which is Bali’s chapter of the National AIDS Commission.
According to the Morning Post, commercial sex work is fueling the spread of HIV/AIDS in Bali, yet mostly local officials refuse to acknowledge like businesses exist. Although sex work is illegal, establishments operate openly in the community or in nightclubs and are patronized by locals and tourists. Deputy Gov. Alit Kesuma Kelakan was ostracized by other officials after proposing to legalize commercial sex, the Morning Post reports. Kelakan said he made his proposal in order to “take a humanitarian perspective on this problem,” adding, “What I’m doing is to implement stricter monitoring of the areas already known for such activities, in arrange to limit” the spread of HIV.
KPAD Bali Founder and Director Dewa Nyoman Wirawan said a foundation survey last year estimated that at least 8,800 sex workers operated in Bali and that up to 14% of them had contracted HIV. He said that sex workers in Bali have a patron base of about 85,000 people and that most customers refuse to wear condoms. The research in addition showed that 8% of sex workers know hither and thither the importance of using a condom, Wirawan said.
KPAD Bali and Kelakan are working together on a program that provides education, obstruction measures, healing attention and other carry to sex workers. Kelakan said the program provides HIV/AIDS education, condoms and no-cost health checkups to sex workers. “We cannot wait for people to die first, and therefore set up a prevention program,” Wirawan said (Scarpello, South China Morning Post, 3/11).
Reprinted with kind permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, make inquiry the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
PPAC Leader Calls Lawsuit Alleging Group Overcharged For Oral Contraceptives ‘Completely False’
Kathy Kneer, president and CEO of Planned Parenthood Affiliates of California, released a statement Tuesday denying allegations in a lawsuit that PPAC overcharged the government for oral contraceptives, the Los Angeles Times reports. Kneer said the allegations are “completely misleading,” adding that California officials “thoroughly reviewed our billing practices and said that Planned Parenthood did not act improperly because we were given contradictory guidance on billing from the state” (Ornstein, Los Angeles Times, 3/12).
The lawsuit was filed by Victor Gonzalez, former vice president of finance and administration of Planned Parenthood Los Angeles. Gonzalez alleges that Planned Parenthood overcharged the state and federal governments by $180 million for birth control pills. An official at the state Department of Health Care Services said that the organization does not indigence to repay any funds even now reimbursed by California because the state’s own rules were unclear (Daily Women’s Health Policy Report, 3/11).
Reprinted with kind permission from http://www.nationalpartnership.org. You can view the entire Daily Women’s Health Policy Report, search the archives, or sign up despite email delivery here. The Daily Women’s Health Policy Report is a free business of the National Partnership for Women & Families, published by The Advisory Board Company.
&transcript; 2007 The Advisory Board Company. All rights reserved.
Soy Compound May Halt Spread Of Prostate Cancer
A compound found in soybeans almost completely prevented the spread of human prostate cancer in mice, according to a study published in the March 15 issue of Cancer Research, a journal of the American Association with regard to Cancer Research.
Researchers say that the amount of the chemical, an antioxidant known as genistein, used in the experiments was not one higher than what a human would eat in a soybean-rich diet.
Investigators from Northwestern University found that genistein decreased metastasis of prostate cancer to the lungs by means of 96 percent compared with mice that did not eat the compound in their chow - making the study the first to demonstrate genistein can stop prostate cancer metastasis in a living organism.
“These impressive results give us hope that genistein might show some effect in preventing the spread of prostate cancer in patients,” said the study’s senior investigator, Raymond C. Bergan, MD, director of experimental therapeutics for the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
“Diet can affect cancer and it doesn’t do it by means of magic,” Bergan said. “Certain chemicals have wholesome effects and now we have all the preclinical studies we need to suggest genistein might be a very promising chemopreventive drug.”
Bergan and his team have previously demonstrated in prostate cancer cell cultures that genistein inhibits detachment of cancer cells from a primary prostate tumor and represses cell invasion. It does this by blocking activation of p38 MAP kinases, molecules which regulate pathways that activate proteins that loosen cancer cells from their tight hold within a tumor, pushing them to migrate. “In culture, you can actually see that when genistein is introduced, cells flatten themselves in order to spread out and stick strongly to nearby cells,” he said.
In this study, investigators fed genistein to several groups of mice before implanting them with an aggressive cast of prostate cancer .The footing up of genistein in the mettle of the animals was comparable to human blood concentrations after consumption of soy foods, Bergan said.
The researchers found that while genistein didn’t reduce the size of tumors that developed within the prostate, it stopped lung metastasis almost completely. They repeated the experiment and mould the same result.
They then examined tissue in the animals, measuring the size of tumor cells’ nuclei to determine if the cells had flattened out in sub-class to spread. “Within a tumor, it is hard to tell where the borders of cells stop, so one way to measure adherence is to look at the size of the nuclei in cells and see if they are wider proper to simplest organism spread,” Bergan said. “And that is what we found, demonstrating that the drug is having a primary effect on metastasis.”
He said that the study also found that mice fed genistein expressed higher levels of genes that are involved in cancer cell migration which, Bergan says, at first might not make sense in light of the study’s conclusion that genistein almost completely blocked metastasis.
“What we think is happening in the present state is that the cells we put in the mice normally like to move. When genistein restricted their ability to do so, they tried to compensate by the agency of producing more protein involved in migration. But genistein prevented those proteins from being activated,” he said. “This is really a lesson for researchers who depend on biomarker studies to test whether a treatment is working. They need to be aware that those biomarkers might be telling only half of the story.”
Bergan cautioned that much is unknown about use of genistein in preventing cancer spread. For example, it may be that the effects of the compound in people who have eaten soy all their lives is stronger than benefit seen in patients who have only started to use genistein.
“The problem we have faced is that epidemiology studies that found men who eat soy are at reduced risk of prostate cancer death are all associative. They don’t prove anything,” he said. “The only way we will find out to what extent promising genistein is will be from conducting clinical trials.”
Human observational studies be under the necessity mould that while the spread of prostate cancer is reduced in men who eat soy-rich foods, findings have been mixed as to whether prostate cancer incidence is markedly contrary. Results of some laboratory studies of genistein have in like manner been mixed, but most have shown favorable results, Bergan said, demonstrating that genistein can inhibit a variety of cell molecules including tyrosine kinases, which activate proteins through attaching them to phosphate chemicals.
A Veterans Administration Merit Award supported the study.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 27,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the stoppage, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, commendable research grants. The AACR Annual Meeting attracts more than 17,000 participants who distribute the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention investigation, is the only journal worldwide dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. CR provides a forum for sharing essential, evidence-based knowledge and perspectives on progress in cancer research, survivorship, and advocacy.
American Association with regard to Cancer Research
Beyond The Abstract Mayo Clinic Validation Of The D’Amico Risk Group Classification For Predicting Survival Following Radical Prostatectomy
UroToday.com - The study here externally validates the potency of the D’Amico risk group classification to predict clinical progression as fully as cancer-specific and overall survival for RRP using the largest series of surgical patients (7,591) evaluated using this model to date. As predictive models use retrospective analyses to prospectively predict the clinical outcome of patients who have not yet been treated, validation is an important mechanism to ensure that such models are able to predict the outcome for patients outside of the original dataset.
The study also demonstrates that RRP achieves durable local control and long-term CSS (median follow-up 7.7 years), even in patients classified as having high-risk disease. Primary surgical therapy for these patients moreover offers the ability to obtain accurate pathological information which may assist in the election of patients for adjuvant therapies who might benefit the most from such treatments, and may elude the application of these potentially harmful therapies to patients not likely to benefit from them.
Overall, this study demonstrates the continued value of the D’Amico danger group classification at the same time that a simple pretreatment prognostic model, based upon clinical features readily available to the treating physician, which may be valuable for patient counseling, to assist with the identification of potential candidates for multimodal treatments, and to ensure the comparability of treatment and control groups in clinical trials.
Written by the agency of Michael L. Blute, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a manner of publishing for the professional urology community. Authors are given an suitable to expand on the circumstances, limitations, etc., of their research by referencing the published abstract.
UroToday - the only urology website with original content written by the agency of global urology key opinion leaders actively engaged in clinical application.
To accession the latest urology news releases from UroToday, go to: www.urotoday.com
Copyright © 2008 - UroToday
China Will Not Consider Changes To One-Child Policy For At Least 10 Years, Official Says
China’s National Population and Family Planning Commission Minister Zhang Weiqing steady Monday said the country would not change its one-child-per-family policy as being at least 10 years, the Wall Street Journal reports (Chao, Wall Street Journal, 3/11). Speculation arose in recent weeks that officials were considering significantly changing the discretion after Zhao Baige, a vice minister in the national family planning commission, was quoted as saying that China was studying by what mode it could move at a distance from the one-child policy. Zhang said that such changes would cause “serious problems,” as well as strain economic and social growth in the country. “Given such a large population base, there would be major fluctuations in population growth if we abandoned the one-child rule now,” Zhang said.
The discretion limits most urban couples to one child and most rural couples to two children, the New York Times reports. According to the Times, critics of the policy say it has led to “numerous abuses,” including forced abortions. The policy also is considered to have contributed to China’s gender imbalance. China is currently the most populous country, with 1.3 billion people. The China Daily reported that the population is growing at 17 million people a year. Government officials have said that the one-child policy has prevented about 400 million births, although some independent scholars have placed the level at closer to 250 million (Yardley, New York Times, 3/11).
Zhang said the one-child limit is strictly enforced among only 35.9% of the populousness living in large cities. He added that the 52.9% of the population living in rural areas have power to have two children if their in the first place child is a girl and that 11% of the population, mostly ethnic minorities, can have two or more children (York, Globe and Mail, 3/11). Zhang said that officials might consider a change in the policy “if there is need” after an anticipated “birth peak” above the next decade, when 200 million people in the country are expected to enter childbearing years.
According to the AP/Boston Herald, the total fertility rate in China is 1.8 children per couple, under the replacement level of 2.1 children per couple (AP/Boston Herald, 3/10).
Reprinted with kind permission from http://www.nationalpartnership.org. You can view the entire Daily Women’s Health Policy Report, search the archives, or sign up for email speech here. The Daily Women’s Health Policy Report is a free service of the National Partnership for Women & Families, published by The Advisory Board Company.
© 2007 The Advisory Board Company. All rights reserved.
Diet And Colorectal Cancer Risk
According to Heinz-Josef Lenz, M.D., professor of medicine, Keck School of Medicine, USC and the USC/Norris Comprehensive Cancer Center, diet may have a major impact on lower classes’s risk of developing cancer. Colorectal cancer is the third most-common cause of cancer-related death in men and women in the nation.
The most important risk factor is red meat, particularly beef, he says. The countries with the highest beef consumption are the ones with the highest colon cancer risk. White meat such as chicken and pork don¹t seem to be associated with colon cancer risk.
Alcohol consumption is another major expose to danger commission merchant, particularly for women, Lenz notes. To restore risk, people should limit themselves to one glass of wine per lifetime.
Avoiding alcohol and decreasing intake of red meat can decrease your risk of colon cancer significantly, he says.
People should be under the necessity rich sources of calcium intake, such as dairy products, diurnal. It is also important to include fiber-rich foods such in the same manner with fruits and vegetables and reduce intake of fatty foods. One of the most powerful ways to reduce colon cancer development is vitamin D and calcium.
With easy adjustments in your diet, supplements such as calcium and modest exercise you can shape your risk of colon cancer by more than 50 percent,² says Lenz.
For more information on colorectal cancer, visit Dr. Lenz¹s blog at www.revolutionhealth.com/pages/colon-cancer
Sequence Of Treatments May Induce Clinical Response In Metastatic Renal Cell Carcinoma Patients
Several recently approved agents offer promising treatment possibilities for patients with metastatic renal cell carcinoma (RCC) and the subordinate class in which these agents are administered may positively impulse clinical response, according to a presentation given during the National Comprehensive Cancer Network (NCCN) 13th Annual Conference: Clinical pursuit Guidelines & Quality Cancer Care™.
Until recently, there were very few agents to treat RCC and those available caused significant side effects. With the approval of agents such as sunitinib, sorafenib, temsirolimus and eventually bevacizumab, patients now have to a greater degree manipulation options, according to Roberto Pili, MD, Associate Professor of Oncology and Urology at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland.
Researchers have observed that some patients continue to demonstrate clinical benefit when they are given these drugs in sequences despite the often met with biological target of these treatments. While no magic combination has yet been codified, researchers hope to determine optimal sequences and combinations of drugs to maximize patient survival.
“We can envision several conspiracy strategies to treat kidney cancer patients,” Dr. Pili said. In addition, “There are several drugs and agents still in development for the treatment of kidney cancer that potentially may offer some promise.” Dr. Pili suggested that combination and sequence strategies may in addition soon include agents like the pan VEGF receptor tyrosine kinase inhibitors axitinib and pazopanib, both of which are currently being studied in ongoing clinical trials.
About the National Comprehensive Cancer Network
The National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 21 of the world’s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health worry delivery order. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives.
For more information, visit http://www.nccn.org.
The NCCN Member Institutions are: City of Hope, Los Angeles, CA; Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Comprehensive Cancer Center, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; Arthur G. James Cancer Hospital & Richard J. Solove Research Institute at The Ohio State University, Columbus, OH; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Memorial Sloan-Kettering Cancer Center, New York, NY; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Roswell Park Cancer Institute, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children’s Research Hospital/University of Tennessee Cancer Institute, Memphis, TN; Stanford Comprehensive Cancer Center, Stanford, CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; UNMC Eppley Cancer Center at The Nebraska Medical Center, Omaha, NE; The University of Texas M. D. Anderson Cancer Center, Houston, TX; and Vanderbilt-Ingram Cancer Center, Nashville, TN.
National Comprehensive Cancer Network
Scottsdale Medical Imaging Participates In National Colon Cancer Study
In the wake of the American Cancer Society’s new guidelines on colon cancer screening, Scottsdale Medical Imaging (SMIL) announces that the organization was a leading participant in the largest multi-center national study comparing virtual colonoscopy with conventional colonoscopy.
The preliminary results of the study show that virtual colonoscopy is as effective in detecting polyps and cancers as conventional colonoscopy. Complete results from the cogitation will be disclosed later this year.
“While the recent innovation in colon cancer screening is very exciting, more importantly I want people to just realize the importance of being screened for the disease,” said Dr. Mark Kuo, SMIL cross-sectional body imaging radiologist and SMIL’s principal investigator for the virtual colonoscopy trial.
“There are some advantages to virtual colonoscopy, including being less invasive, no requirement for sedation and a minimal time commitment. Virtual colonoscopy can be a more comfortable procedure than conventional colonoscopy,” adds Kuo.
Colon cancer is the second leading attempt of cancer-related deaths in the United States. The American Cancer Society estimates that 950 people will die in Arizona this year from illnesses related to colon cancer. It is recommended that people age 50 and over get a colon cancer screening (at intervals of five to 10 years). People with a family history of colon cancer, who suffer from inflammatory bowel malady or who have had a polyp before, are at higher risk and are urged to have existence screened.
The significance of colon cancer screening is often overlooked. Studies pomp colon cancer screenings can save lives. If caught early, colon cancer is one of the most preventable, treatable cancers today, having a 90 percent survival rate. However, only moiety of the people recommended to receive screenings actually do such. The bottom line - get screened before it’s too late.
During March’s Colorectal Cancer Awareness Month, SMIL is urging Valley residents to see their physician about colon cancer screening.
About SMIL
Founded 26 years gone, Scottsdale Medical Imaging (SMIL), affiliated with Southwest Diagnostic Imaging, Ltd., is the most respected radiology frequent repetition in the southwest and human being of Arizona’s largest. Owned and operated by 45 board-certified radiologists, SMIL has 10 imaging centers with more than 300 technologists and para-medical personnel providing expertise in a wide range of modalities and clinical areas including body imaging, MRI, CT, PET-CT, oncologic radiology, interventional, ultrasound and breast imaging. SMIL proudly sustains a cutting-edge research department that specializes in improving patient care and uncovering innovative techniques in the field of radiology.
Scottsdale Medical Imaging
Airlines Should Upgrade Medical Emergency Protocol
Medical emergency protocols should be upgraded and optimised on wholly major airlines, argues a doctor in this week’s BMJ.
Osman Dar, a clinical fellow at Addenbrooke’s Hospital in Cambridge shares his experience of treating an elderly man with crushing chest pain on a flight to Africa.
He describes how the medical equipment was limited and how, on landing, the crew did not announce that an ill uncomplaining was on board who needed priority evacuation from the plane. And, although the pilot radioed ahead for an ambulance to transfer the passenger to a hospital , the ground staff did not have the means or the easiness to arrange single, so when they landed there wasn’t undivided present.
"What I experienced can only be described as a catalogue of failures by a reputable airline," he says.
With the advent of telemedicine and the availability of automated external defibrillators (AEDs), no reason exists now why a suitably trained doctor on the ground cannot at least communicate basic life support transactions to aircraft crew or even advise the captain to request one emergency landing, he writes.
grant that cost implications are an delivering for airlines around the world, a proactive policy rather than a reactive one seems sensible, he says. The United States, for example, has mandated AEDs on aggregate airlines since 2004. He also suggests basic minimal standards for medical kits on all planes on all routes and complete audits to improve and individualise them. BMJ looks at how common in-flight medical emergencies are and what doctors are expected to do in such circumstances.
No commentsNIST Microscope Tracks Nanoparticles In 3-D
A clever new microscope design allows nanotechnology researchers at the National Institute of Standards and Technology (NIST) to track the motions of nanoparticles in solution as they dart around in three dimensions. The researchers hope the technology, which NIST plans to patent, will lead to a better understanding of the dynamics of nanoparticles in fluids and, ultimately, process control techniques to optimize the assembly of nanotech devices.
While some nanoscale fabrication techniques borrow from the lithography and solid state methods of the microelectronics industry, an equally promising approach relies on “directed self-assembly.” This capitalizes on physical properties and chemical affinities of nanoparticles in solutions to induce them to gather and arrange themselves in desired structures at desired locations. Potential products include extraordinarily sensitive chemical and biological sensor arrays, and new medical and diagnostic materials based on “quantum dots” and other nanoscale materials. But when your product is too small to be seen, monitoring the assembly process is difficult.
Microscopes have power to help, but a microscope sees a three-dimensional fluid volume as a 2-D level. There’s no real sense of the “up and down” movement of particles in its field of view except that they get greater amount of or less fuzzy as they move across the even where the instrument is in focus. To date, attempts to get ready a 3-D view of the movements of nanoparticles in solution largely have relied on that fuzziness. Optics theory and mathematics can estimate how far a particle is above or under the focal level based on diffraction patterns in the fuzziness. The math, however, is extremely difficult and time consuming and the algorithms are imprecise in practice.
One alternative, NIST researchers reported at the annual meeting of the American Physical Society,* is to use geometry instead of algebra. Specifically, angled side walls of the microscopic sample well act as mirrors to reflect side views of the volume up to the microscope at the same time as the top view. (The typical sample well is 20 microns square and 15 microns deep.) The microscope sees each particle twice, one image in the horizontal plane and one in the vertical. Because the two planes have one dimension in worn out, it’s a simple calculation to correlate the two and figure out each particle’s 3-D path. “Basically, we reduce the problem of tracking in 3-D to the problem of tracking in 2-D twice,” explains lead author Matthew McMahon.
The 2-D problem is simpler to solve - several software techniques can calculate and track 2-D situation to better than 10 nanometers. Measuring the nanoparticle motion at that fine scale - speeds, diffusion and the like - will allow researchers to calculate the forces acting on the particles and better see the basic rules of interaction between the various components. That in turn will allow better design and control of nanoparticle assembly processes.
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Article adapted by dint of. Medical News Today from original press release.
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* M. McMahon, A. Berglund, P. Carmichael, J. McClelland and J.A. Liddle. Orthogonal tracking microscopy for nanofabrication research. Paper presented March 10, 2008, 1:03 p.m., at the 2008 March Meeting of the American Physical Society, New Orleans, La., March 10-14, 2008.
Source: Michael Baum
National Institute of Standards and Technology (NIST)
Structure Reveals How Cells ‘Sugar-Coat’ Proteins
Biologists at the U.S. Department of Energy’s Brookhaven National Laboratory, Stony Brook University, and the University of Wurzburg, Germany, have deciphered the structure of a large protein complex responsible for adding sugar molecules to newly formed proteins - a process essential to many proteins’ functions. The structure offers discernment into the molecular “sugar-coating” mechanism, and may help scientists better understand a diversity of diseases that result when the process goes awry. The research will appear in the March 12, 2008, issue of the journal Structure.
“Proteins perform their functions by interacting at their surfaces through other molecules. So you can imagine that adding or removing sugar molecules will change the protein’s surface structure, and therefore its function,” said Huilin Li, a biologist at Brookhaven Lab who holds a joint appointment at Stony Brook and is co-corresponding author on the Structure paper. “Messing up this process can lead to the production of malformed proteins that are unable to do their jobs,” he added.
The results can be devastating. Failure of glycosylation, as the “sugar-coating” performance is known, can lead to a variety of genetic disorders characterized through neurological problems including seizures and stroke-like episodes, feeding disorders, and possibly even some forms of muscular dystrophy.
“We studied one enzyme involved in glycosylation, the one that recognizes the protein sequence and adds the sugar chains to the protein as it is inner reality synthesized by the cell,” before-mentioned William J. Lennarz of Stony Brook University, a coauthor on the paper. “The challenge is that the enzyme, known as oligosaccharide transferase (OT), is large by protein standards, has eight intricately linked components, and sits embedded in a membrane within the cell’s protein-manufacturing mechanism.”
“Membrane proteins, particularly large ones, are very difficult to study structurally,” added Li.
So the scientists turned to a technique called cryo-electron microscopy (cryo-EM), which shows great promise in deciphering immense membrane protein structures.
“We imaged the purified OT complex by cryo-EM and obtained a leading snapshot of the complex by computer reconstruction of the micrographs,” said Li, a cryo-EM expert.
In cryo-EM, he explained, samples are frozen in glassy ice and maintained at cryogenic temperatures (-274° Fahrenheit) using liquid nitrogen while the samples are photographed in the high vacuum of an electron microscope. The sophisticated cryo-EM machine resides in Brookhaven Lab’s biology department. Li and his collaborators also measured the mass of the OT complex at Brookhaven’s Scanning Transmission Electron Microscope (STEM) facility.
The structure deciphered by the collection helps to explain many biochemical phenomena observed relative to the enzyme complex over the past two decades. It also offers hints as to how the enzyme performs its various jobs, from recognizing the sugar molecules to be added to the protein, scanning the protein as it is formed to identify the sites where sugars should be attached, and transferring the sugar molecules to the protein at the right positions.
“OT physically associates with the protein translocation channel which moves a protein across a membrane and the cell’s protein synthesis machinery, forming an efficient three-machine assembly line for protein translation, translocation, and glycosylation,” Li said.
The researchers say further research is needed to illuminate the molecular mechanisms of disorders of glycosylation involving oligosaccharide transferase. For example, they would like to do structural studies of the enzyme at higher resolution in complex with substrates or in association with the cell’s protein translocation and protein synthesis machinery. A new facility Brookhaven Lab hopes to begin construction on next year, known as the National Synchrotron Light Source II, would greatly increase the precision of this work.
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Article adapted by Medical News Today from type press release.
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This research was supported through the National Institutes of Health and by Brookhaven National Laboratory’s Laboratory-Directed Research and Development funds.
common of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as fountain as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE’s Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.
Source: Karen McNulty Walsh
DOE/Brookhaven National Laboratory
Hepatitis E Virus Research Goal Is The Development Of Human, Animal Vaccine
Dr. X.J. Meng, of Blacksburg, Va., a professor of virology in the Virginia-Maryland Regional College of Veterinary Medicine’s Department of Biomedical Sciences and Pathobiology at Virginia Tech, has been awarded two research grants totaling almost $3 million from the National Institutes of Health (NIH) to study the hepatitis E poison (HEV). The ultimate goal of the work is to develop a vaccine to protect people and animals from Hepatitis E.
HEV is an important like a man pathogen, according to Meng. The disease caused by HEV, Hepatitis E, is a major public health problem in developing countries in Asia and Africa, and in Mexico. Hepatitis E is also endemic in the United States and many other industrialized countries, according to Meng. Although the overall mortality associated with HEV infection is generally low (less than 1 percent), it can be of the same kind with high as 28 percent in infected pregnant women. Currently, there is no vaccine to prevent Hepatitis E.
The major obstacle for Hepatitis E research and vaccine development has been the lack of a practical animal model system for HEV research and the inability to propagate HEV in cell culture, explains Meng. With funding from NIH, Meng’s group recently discovered two HEV-related animal viruses in the United States: swine hepatitis E virus (swine HEV) from pigs, and avian hepatitis E virus (avian HEV) from chickens. It has since been demonstrated that swine HEV can cross species barriers and infect humans, and that human HEV can infect pigs. Hepatitis E is now regarded as a zoonotic disease.
With the discoveries of the two unaccustomed animal viruses, Meng’s group quickly developed a pig model and a chicken model to study the hepatitis E virus. Prior to Meng’s discoveries of the two animal hepatitis E viruses, scientists were forced to use non-human primates in mandate to study the disease. Conducting HEV research with primates at one of the NIH regional primate centers is expensive and contains some moral concerns, according to Meng, so developing the new animal models will be a major step forward in the research.
The foremost NIH grant, entitled “Mechanism of hepatitis E virus replication and pathogenesis,” conveys total funding of $1,561,797 and the co-investigators are Dr. Patrick G. Halbur, and Dr. Yao-Wei Huang. The second grant, entitled “A chicken model to study hepatitis E virus pathogenesis” includes funding of $1,266,300 and the co-investigators are Dr. F. William Pierson, Dr. Tanya LeRoith, and Dr. Yao-Wei Huang. Both grants begin on March 1, 2008 and will support four years of work.
The grants will enable researchers to make one’s self acquainted with more about the molecular mechanisms of HEV replication and pathogenesis by using pigs and chickens because animal model systems. Specifically, the researchers will study how HEV causes hepatitis, the gene(s) that are responsible for virulence, the mechanism(s) for cross-species infection by HEV, and how to attenuate the virus for vaccine development purpose. Ultimately, the researchers hope to develop a vaccine against this important human pathogen.
Meng’s laboratory in the college’s Center for Molecular Medicine and Infectious Disease (CMMID) is considered unit of the world’s leading Hepatitis E virus research centers. Previously, he had received nearly $2 million dollars from the NIH to study the same virus. Meng currently chairs the Hepatitis E Virus study group on the International Committee on Taxonomy of Viruses (ICTV).
Funded by the United States Department of Agriculture and several private corporations, Meng’s lab also studies divers economically important animal viruses including porcine circovirues, and porcine reproductive and respiratory syndrome virus. Recently, Meng’s lab successfully developed the first USDA fully-licensed vaccine, Suvaxyn® PCV2 One Dose™, against porcine circovirus associated diseases, an economically important swine disease worldwide. Virginia Tech has licensed the vaccine to Wyeth Inc. and Fort Dodge Animal Health Inc., and the vaccine is currently on the U.S. and Canadian markets, and has now begun to enter the global markets. The vaccine is saving millions of dollars both year for the swine industry.
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Article adapted by Medical News Today from original press release.
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Click here to learn more about Meng’s research.
Prior to joining the college in 1999, Meng served as Senior Staff Fellow of the Molecular Hepatitis Section of the Laboratory of Infectious Diseases at the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID).
Meng earned an M.D. from Binzhou Medical College in Binzhou, Shandong, People’s Republic of China; a M.S. in microbiology and immunology from the Virus Research Institute, Wuhan University College of Medicine, Wuhan, Hubei, Peoples Republic of China; and a Ph.D. in immunobiology from the Department of Microbiology, Immunology and Preventive Medicine at the Iowa State University College of Veterinary Medicine, Ames, Iowa.
The Virginia-Maryland Regional College of Veterinary Medicine (VMRCVM) is a two-state, three-campus professional school operated by the land-grant universities of Virginia Tech in Blacksburg and the University of Maryland at College Park. Its flagship facilities, based at Virginia Tech, include the Veterinary Teaching Hospital, which treats more than 40,000 animals annually. Other campuses include the Marion duPont Scott Equine Medical Center in Leesburg, Va., and the Avrum Gudelsky Veterinary Center at College Park, home of the Center for Government and Corporate Veterinary Medicine. The VMRCVM annually enrolls approximately 500 Doctor of Veterinary Medicine and graduate students, is a leading biomedical and clinical research center, and provides professional continuing cultivation services for veterinarians practicing throughout the two states. Virginia Tech, the most comprehensive university in Virginia, is dedicated to quality, innovation, and results to the commonwealth, the nation, and the world.
Source: Jeff Douglas
Virginia Tech
Stenting And Photodynamic Combined Therapy Improves Survival In Late Stage Liver Cancer Patients
A combined therapeutic approach of stenting and photodynamic therapy may improve survival rates as far as concerns patients suffering from advanced liver bile duct cancer, according to a study published this month in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association (AGA) Institute.
Researchers in the study found that while stenting can help reinforce the bile duct to increase liver functionality, the light therapy assisted in attacking the cancer cells directly. The combined therapy led to significant reductions in mortality rates in the year following treatment, compared with stenting treatment alone.
“This is a very aggressive disease that we’re fighting, as most patients are diagnosed when we can only offer lenitive care,” said Michel Kahaleh, MD, of the University of Virginia and induce investigator of the study. “What we found in this study is that combining therapies that fight the disease and help improve liver functionality can co-operate with increase the survival rates for these patients.”
In this reflection, 48 patients were treated for advanced cholangiocarcinoma over a five year period. Nineteen were treated with photodynamic therapy (PDT) and stents, space of time 29 patients were treated with biliary stents alone. In the group receiving combined therapy, the photodynamic agent (porfimer sodium, a commonly used agent) was injected and activated, and plastic stents were inserted. PDT was repeated every three months, at which time all stents were replaced. If the team found blockages or shifting, stents were exchanged earlier to maintain optimal decompression.
The group treated with stenting and PDT showed improved survival rates compared to the stent-only group (16.2 months vs. 7.4 months). Mortality in the PDT group at three, six and 12 months was 0, 16 and 56 percent respectively, while the corresponding mortality in the stent group was 28, 52 and 82 percent respectively. The difference betwixt the two groups was significant at three and six months, but not at 12 months. Upon further analysis, the team found that only the number of ERCP procedures and number of PDT sessions were significant in determining survival. In both groups, serum bilirubin was successfully reduced.
PDT is an evolving therapy that involves administering a photosensitizing agent and activating it using light illumination of a specific wavelength, which kills the targeted cells. PDT is thought to destroy cancer and neovascular cells and reduce tumor mass, and in earlier prospective trials, PDT was associated with a significant reduction in bilirubin (a red blood lonely dwelling byproduct excreted in liver bile) and increased survival compared to historical data.
“While we are pleased with the results of the study, we need to more valuable understand if the effect is attributable primarily to the photodynamic therapy or to the number of ERCP sessions,” said Dr. Kahaleh.
Adverse events specific to PDT included three patients with skin phototoxicity requiring topical therapy. Complications in the stent-only group included patients developing cholangitis after therapy with two patients dying as a consequence. Post ERCP pancreatitis was observed in four patients and duodenal perforation in one. Other adverse events in the stent group included a liver abscess (1), perforation (1) and non-St elevation myocardial infarction, or heart attack (2). In the PDT group, seven patients (37 percent) developed cholangitis treated with antibiotics alone. No patients had contraindications to photodynamic therapy contrast agents, and all patients received prophylactic antibiotics prior to the procedures.
Analyses were performed to detect predictors of survival, including MELD score (Model for End-stage Liver Disease, the extent of the disease), age, treatment by chemotherapy or radiation, and number of ERCP procedures and PDT sessions. Successful therapy was defined by relief of cholangitis (infection caused by biliary blockage), jaundice and pruritis (itching) with a decrease of bilirubin to less than 75 percent of the pre-treatment value within 30 days.
Cholangiocarcinoma (cancer of the liver’s bile ducts) is the second principally common liver cancer and is associated with significant morbidity and mortality, diagnosed in about 2,000 new cases every year. The majority of patients (almost 80 percent) are diagnosed when surgery is no longer an election fit to the extent of the disease, with most surviving up to three months without intervention or four to six months with decompression treatment, which helps maintain the function of the liver by opening the bile ducts.
Treatment for the disease has evolved from surgery to endoscopic management, that involves placing a plastic stent in the bile duct to manage flow and control the cancerous growth (ERCP). It has become a standard of care to manage jaundice and prevent cholestasis (blockage of the bile duct), by less morbidity and mortality than that associated by surgery. However, the efficacy of stenting is limited because they cannot independently attack the tumor cells.
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Article adapted by Medical News Today from original press release.
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About the AGA Institute
The American Gastroenterological Association (AGA) is dedicated to the mission of advancing the science and practice of gastroenterology. Founded in 1897, the AGA is one of the oldest medical-specialty societies in the U.S. Comprised of two non-profit organizations - the AGA and the AGA Institute - our more than 16,000 members include physicians and scientists who research, diagnose and treat disorders of the gastrointestinal tract and liver. The AGA, a 501(c6) organization, administers all membership and public policy activities, under which circumstances the AGA Institute, a 501(c3) organization, runs the organization’s practice, research and educational programs. On a monthly basis, the AGA Institute publishes two highly respected journals, Gastroenterology and Clinical Gastroenterology and Hepatology. The organization’s annual meeting is Digestive Disease Week®, which is held each May and is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. For more information, content visit http://www.gastro.org/.
About Clinical Gastroenterology and Hepatology
The mission of Clinical Gastroenterology and Hepatology is to provide readers with a unrefined image of themes in clinical gastroenterology and hepatology. This monthly peer-reviewed journal includes original articles as well as scholarly reviews, with the goal that all articles published will be immediately relevant to the practice of gastroenterology and hepatology. For more information, visit http://www.cghjournal.org/.
Source: Aimee Frank
American Gastroenterological Association
Study Helps Explain Fundamental Process Of Tumor Growth
Nearly 80 years ago, scientist Otto Warburg observed that cancer cells perform energy metabolism in a way that is different from normal adult cells. Many decades later, this observation was exploited through clinicians to better visualize tumors using PET (positron emission technology) imaging. But it has not been known exactly how tumor cells perform this alternate metabolic feat, nor was it known if this process was essential for tumor growth.
Now, two papers appearing in the March 13 issue of the journal Nature help respond these questions. Led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School, the papers meet through that the metabolic process that has come to be known as the Warburg effect is essential for tumors’ rapid growth, and identifies the M2 form of pyruvate kinase (PKM2), an enzyme involved in sugar metabolism, as an important mechanism behind this continued movement. This discovery could provide a target for the development of what may occur hereafter cancer therapies.
“With this study we have answered a fundamental subject of investigation regarding the ability of tumor cells to rapidly grow and proliferate,” explains senior author Lewis Cantley, PhD, Director of the Cancer Center at BIDMC and Professor of Systems Biology at Harvard Medical School.
Metabolic regulation in rapidly growing tissues, such as fetal tissue or tumors, is different from that of normal adult tissue, Cantley explains. “Through aerobic glycolysis, or the Warburg effect, cancer cells produce energy by taking up glucose at much higher rates than other cells while, at the similar time, using a smaller fraction of the glucose for energy production. This allows cancer cells to function more in the same manner as fetal cells, promoting extremely rapid growth.” This unique metabolic property of cancer cells has led to the success of PET imaging as a means of cancer detection; because radioactive grape-sugar injected into patients prior to the imaging exam is preferentially taken up by glucose-hungry tumor cells, the areas of high glucose uptake are displayed dramatically on the PET scan.
Using a novel proteomic sift to identify new phosphotyrosine binding proteins, Cantley and his colleagues first determined that PKM2 can bind to phosphotyrosine-containing peptides. “We observed that in contrast to the forms of pyruvate kinase found in principally normal adult tissues, only PKM2, which is found in fetal cells, interacted with phosphotyrosine,” explains Cantley. “This finding was particularly interesting because previous reports had shown that this M2 form was the pyruvate kinase form used by all cancer cells.”
In order to understand the implications of this discovery, Cantley and his coauthors next embarked upon experiments to evaluate the importance of PKM2 to cancer cells. Reasoning that tumor tissue switches pyruvate kinase expression from an adult M1 isoform to the embryonic M2 isoform, they performed immunoblotting and immunohistochemistry analysis of numerous cancer cell lines, affections cancer models and human colon cancer, confirming that PKM2 was the only form of pyruvate kinase found in cancerous tissue.
The authors then knocked down PKM2 expression in human cancer cell lines and expressed the adult M1 form instead. This switch from the fetal M2 form to the adult M1 isoform led to reduced lactate production and increased oxygen consumption a reversal of the Warburg effect.
“We were able to show that only cells which express the M2 form of pyruvate kinase and metabolize glucose in the way described through Otto Warburg 80 years ago had the ability to form tumors in mice,” notes Cantley. In addition, the investigators demonstrated that it is the ability of PKM2 to interact with phosphotyrosine that enables this form of pyruvate kinase to promote the unique glucose metabolism seen in cancer cells, thereby allowing these cells to make tumors in vivo.
The findings are consistent with the idea that tumor cells preferentially use glucose for purposes other than making adenosine triphosphate (ATP), the energy currency used by dint of. normal cells. “We suspect that this mechanism evolved to ensure that fetal tissues only use glucose for growth when they are activated by the agency of appropriate growth factor receptor protein-tyrosine kinases,” adds Cantley. “By re-expressing PKM2, cancer cells acquire the might to exercise glucose for anabolic processes.
“Because PKM2 is found in all of the cancer cells that we have examined, because it is not found in most normal adult tissues, and because it is critical for tumor formation, this form of pyruvate kinase is a possible target during the term of cancer therapy,” he adds.
This research was funded by grants from the National Institutes of Health and the Damon Runyon Cancer Research Foundation.
Coauthors of the Nature article “Pyruvate kinase M2 is a phosphotyrosine binding protein,” include leadership author Heather Christofk, of Harvard Medical School (now at UCSF Cancer Research Institute); Matthew Vander Heiden of the Dana-Farber Cancer Institute; Ning Wu of Harvard Medical School; and John Asara of Beth Israel Deaconess Medical Center. Coauthors of the second Nature paper, “The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth,” include Christofk (lead author) and Vander Heisen; Marian Harris and Mark Fleming of Children’s Hospital Boston; and Arvind Ramanathan, Robert Gerszten, Ru Wei and Stuart Schreiber of the Broad Institute, Cambridge, Mass.
Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks in the top four in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www.bidmc.harvard.edu.
Harvard Medical School has more than 7,500 full-time faculty working in 11 academic departments located at the School’s Boston campus or in one of 47 hospital-based clinical departments at 17 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Cambridge Health Alliance, Children’s Hospital Boston, Dana-Farber Cancer Institute, Forsyth Institute, Harvard Pilgrim Health Care, Joslin Diabetes Center, Judge Baker Children’s Center, Immune Disease Institute, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye investigation Institute, Spaulding Rehabilitation Hospital, and VA Boston Healthcare System.
Beth Israel Deaconess Medical Center
330 Brookline Ave.
Boston, MA 02215
United States
http://www.bidmc.harvard.edu
Gene Therapy Could Save Kids With Rare Metabolic Disorder From A Lifetime Of Eating Cornstarch
A gene therapy treatment that restores a missing liver enzyme in test animals could provide a cure for a rare metabolic disorder in humans, according to Duke University Medical Center researchers.
People born with the disorder, called glycogen storage disease type 1a (GSD-1a), be able to’t make an enzyme that helps the liver store and release glucose, the sugar that all cells use for energy. Without treatment, their blood sugar levels drop dangerously low, causing seizures and organ damage. Eating raw cornstarch, a slowly digested carbohydrate, and avoiding dietary sugar can help people with GSD-1a maintain their glucose levels. However, even a peculiar take nourishment does not prevent the eventual liver impair that results from the absent enzyme, and many adults with the disease develop liver and kidney failure or liver cancer. With treatment, most people with GSD-1a have a relatively normal lifespan
The gene therapy developed at Duke would give liver cells the correct genetic code for manufacturing the enzyme. A modified virus transfers the enzyme genes by infecting liver cells. The venom is not linked to any known human disease, and cannot copy itself and spread to other people, said medical geneticist Dwight Koeberl, M.D., Ph.D., lead study author and an associate professor in the Department of Pediatrics.
The research involved creating a virus so focused on targeting liver cells that only a tiny amount is needed for treatment, minimizing potential side effects. Showing that the venom is safe and effective in small doses is an important step in bringing the treatment to clinical trials in humans.
The gene therapy replaced the missing enzyme in the liver to fully normal levels, and protected both mice and dogs with the disease from low blood glucose for up to a year. “No one has fully corrected the enzyme that produces glucose in the liver before. We think we can correct every cell in the liver,” Koeberl said.
The results appear in the March 11 2008 issue of the journal Molecular Therapy. The research was funded by the Children’s Fund with respect to GSD Research, the Association for Glycogen Storage Disease and the Duke Children’s Miracle Network. Dr. Emory and Mrs. Mary Chapman, and Dr. and Mrs. John Kelly, families of a child with GSD-Ia, also provided support.
The researchers tested the technique on mice bred without the genetic code to make the enzyme, as well as young dogs with a naturally-occurring canine form of glycogen storage disease. The original genetic carrier, a Maltese, was identified by a Georgia breeder, and veterinarians at North Carolina State University College of Veterinary Medicine have worked with Duke to maintain a population of dogs with the disease since the mid-1990s.
The success of the new treatment makes the therapy worth testing in long-term creature studies, Koeberl said. “This is a step along the way toward developing a curative therapy for our patients,” he said. The key is finding funding for a years-long trial. “There are not a lot of companies developing treatments for rare diseases,” he added.
GSD-Ia occurs in about one of every 100,000 births in the U.S. Duke is treating about 100 patients with the ail.
A long-term study would demonstrate whether gene therapy can prevent complications such as kidney failure and liver cancer, which develop even if people strictly hinder their diet and blood sugar levels. Other problems associated with the disease include growth restriction, high blood pressure, pancreatitis and persistent hypoglycemia.
“There are definite well-documented limitations to the dietary therapy. People can’t just follow a diet and count on living full, healthy lives,” Koeberl reported.
Lengthy trials are also necessary because the corrected genes don’t transfer when liver cells divide and copy themselves. However, the slow rate at which liver cells divide means the treatment may be effective for many years, with only a few boosters needed during an individual’s lifetime, Koeberl said.
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Article adapted by Medical News Today from original press release.
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Study co-authors contain Baodong Sun, Songtao Li, Danny Benjamin Jr., Steven Hillman, Andrew Bird, Priya Kishnani and Y.T. Chen, all of Duke; Carlos Pinto, Daniel Kozink, Talmage Brown, Amanda Demaster and Meghan A. Kruse, totality of North Carolina State University; Valerie Vaughn at the University of Michigan Medical School; and Mark Jackson at the University of Glasgow, Scotland.
Source: Debbe Geiger
Duke University Medical Center
Progen Announces Commencement Of Global Phase 3 Study For PI 88 In Post Resection Liver Cancer
Progen Pharmaceuticals Limited (ASX: PGL; Nasdaq: PGLA) announced the commencement of its global phase 3 study investigating PI-88 as an adjuvant treatment for primary liver cancer (hepatocellular carcinoma, HCC) following curative resection with the first patient having been randomized onto the study. The study is known globally as PATHWAY (PI-88 in the adjuvant treatment of HCC). The first patient to enter the trial is from Singapore.
Dr. Ronnie Poon, Ph.D., M.D., global lead investigator for PATHWAY, commented, “My colleagues and I are encouraged through the phase 2 data that Progen has generated for PI-88 in this challenging disease, for that there are no approved treatment options. If PATHWAY is successful, PI-88 could change the standard of care for resected liver cancer patients.”
PATHWAY, a double-blinded, placebo-controlled research, has been designed to establish the efficacy and safety of PI-88 in the post resection liver cancer setting. The trial will recruit approximately 600 patients at about 65-70 hospitals in more than a dozen countries. Disease-free survival, a measure of the average length of time that patients remain free of tumor recurrence, is the primary endpoint. Upon completion of this trial, the results are expected to form the basis of global registration filings for PI-88.
Justus Homburg, Progen’s CEO, said, “Commencement of this trial represents a significant milestone for Progen. We have designed this trial in collaboration with world experts in this field of medicine, and with USA FDA Fast Track and EU EMEA Orphan Drug Status, its initiation underscores our commitment to making this important drug rapidly available to patients who currently have few treatment options available.”
Liver cancer is one of the top five causes of cancer deaths in the world, with over half a million new cases per year. Although surgical resection is one of the few treatment options by curative potential, recurrence is common within the first 12 to 15 months following surgery and five-year survival following resection is less than 50%.
Dr. James Garner, Progen’s Vice President of Clinical and Medical Affairs, added, “Since the release of our promising phase 2 given conditions last year, our team has worked tirelessly to design a world-class phase 3 trial for PI-88 in liver cancer. We are very thankful for the support of key opinion leaders and clinicians all over the world, many of whom will now be serving as investigators in PATHWAY. While the study is starting later than we had hoped as a result of some delays opening sites due to a greater-than-expected impact from holidays over the past couple of months, Progen continues to aggressively take in a carriage country regulatory and hospital ethics approvals to conduct this phase 3 trial.”
The study now has regulatory approval in almost half of the participating countries and more than a dozen sites have been granted approval by ethics committees. Sites are being initiated so as to subsist able to commence patient recruitment as soon while these necessary approvals have been granted.
About PI-88: PI-88 is one of a new class of multi-targeted cytostatic cancer therapeutics. It is a rare anti-cancer compound with a first-in-class mechanism as a heparan sulfate mimetic. Its anti-tumor activity is based on check of two biological processes — angiogenesis (the growth of renovated blood vessels) and metastasis (the spread of cancer to other sites) — critical to the growth and progression of cancer. In April 2007, data from a randomised phase 2 trial in the post resection liver cancer setting was presented at the European Association for the Study of the Liver (EASL) meeting in Barcelona, Spain. PI-88, in this disease setting, has been granted Orphan Drug designation by the European Medicines Evaluation Agency (EMEA) and Fast Track designation by the United States Food and Drug Administration (FDA). These results provide Progen with confidence in the in posse of PI-88 for this indication and we are therefore aggressively pursuing its development towards registration and commercialization.
About the phase 3 study: The phase 3 study investigating PI-88 as a post- resection treatment for hepatocellular carcinoma (HCC, primary liver cancer) following curative resection is a double-blinded, placebo-controlled study that has been designed to establish the efficacy and safety of PI-88 in the post-resection HCC setting. The trial will recruit approximately 600 patients at 65-70 hospitals in added than a dozen countries. Disease-free survival is the study’s primary endpoint. Upon completion of this trial, the results are expected to form the basis of global regulatory filings for PI-88.
About Progen: Progen Pharmaceuticals is a globally focused biotechnology company committed to the discovery, development and commercialization of small molecule pharmaceuticals primarily for the treatment of cancer. Progen has operations in Australia and the US.
This press release contains forward-looking statements that are based on current management expectations. These statements may bicker materially from actual denoting futurity events or results due to certain risks and uncertainties, including without limitation, risks associated with drug development and manufacture, risks inherent in the extensive regulatory approval process mandated by the United States Food and Drug Administration and the Australian Therapeutic Goods Administration, delays in obtaining the necessary approvals for clinical testing, patient recruitment, delays in the conduct of clinical trials, market acceptance of PI-88, PI-166 and other drugs, future capital needs, general economic conditions, and other risks and uncertainties detailed from time to time in the Company’s filings with the Australian Securities Exchange and the United States Securities and Exchange Commission. Moreover, there can subsist no assurance that others will not independently develop similar products or processes or design around patents owned or licensed by the Company, or that patents owned or licensed by the Company will provide meaningful bulwark or competitive advantages.
Progen Pharmaceuticals Limited
http://www.progen.com.au