Vertex books bigger 4Q loss on research costs
Feb 3, 2011 6:13 PM ET By The Associated Press
CAMBRIDGE, Mass. (AP) — Vertex Pharmaceuticals Inc. reported a larger fourth-quarter loss on Thursday as it spent more money to develop its hepatitis C drug candidate telaprevir, along with a potential cystic fibrosis treatment and other drugs.
With its research and development costs up 25 percent, Vertex said it lost $180.4 million, or 90 cents per share, in the last three months of 2010. A year ago it booked a smaller loss of $158.6 million, or 86 cents per share. Revenue nearly doubled to $65.5 million from $33.9 million.
Analysts had expected a loss of 92 cents per share and $38.8 million in revenue, according to FactSet.
Vertex has applied for marketing approval of telaprevir in the U.S., Europe, and Canada. The Food and Drug Administration is expected to make a decision by May 23. Vertex is also waiting for data from a late-stage clinical trial of VX-770, its cystic fibrosis drug, and running a mid-stage clinical trial of a regimen that combines telaprevir with another one of its hepatitis C drug candidates, VX-222. The company expects results from that study later in the first quarter.
Vertex said it plans to file for approval of VX-770 in the U.S. and Europe in the second half of 2011.
The company said its research and development costs climbed to $168.9 million from $135.2 million a year ago. However revenue from partnerships more than doubled to $57.1 million from $25.5 million. Royalty revenue was unchanged at $8.4 million.
For the full year, Vertex lost $754.6 million, or $3.77 per share, compared with a loss of $642.2 million, or $3.71 per share, in 2009. Revenue grew 41 percent, to $143.4 million from $101.9 million.
"We believe that our financial position will support our key business objectives through 2012, at which time we expect to begin generating earnings as a cashflow positive company," said Matthew Emmens, chairman, president and CEO, in a statement.
Shares of Vertex fell 17 cents to close at $38.80 on Thursday.
http://www.bloomberg.com/news/2011-02-03/vertex-books-bigger-4q-loss-on-research-costs.html
Thursday, February 3, 2011
Hepatitis C;Tacere Therapeutics Reacquires Rights to Develop and Commercialize its HCV Compounds in Asia
Tacere Therapeutics Reacquires Rights to Develop and Commercialize its Hepatitis C Compounds in Asia
SAN JOSE, Calif., Feb. 3, 2011 /PRNewswire/ -- Tacere Therapeutics, Inc., an RNA interference (RNAi)-based therapeutics company, announced today that it has reacquired the development and commercialization rights to its Hepatitis C Virus (HCV) compounds throughout Asia from its strategic partner, Tokyo-based Oncolys BioPharma Inc.
"We are very happy to have regained control of the Asian development and commercialization rights to our family of HCV compounds," said Sara Hall Renison, Chief Executive Officer of Tacere. Mike Catelani, Chairman, President and CFO, added, "With the continued promising development of our lead HCV compound in partnership with Pfizer, holder of the non-Asian worldwide development and commercialization rights, we believe that we are well-positioned to commence regulatory activities in Asia."
About Tacere's family of HCV compounds
Tacere's family of HCV compounds, are novel therapeutic products containing three separate RNAi elements targeted against the Hepatitis C virus itself and encapsidated in an adeno-associated virus (AAV) protein coat. AAV delivery methods have demonstrated clinical safety, and preclinical animal studies with TT-034, the lead compound in the family, have shown the ability to penetrate hepatocytes (the site of HCV replication) at high levels following a single intravenous administration. In preclinical animal studies, this "cocktail in one drug" monotherapy targeted and cleaved the Hepatitis C virus itself at three different sites simultaneously without toxicity.
About Tacere Therapeutics, Inc.
Tacere is an innovative biotechnology company focused on developing therapeutics to treat human diseases using its proprietary knowledge in the development of RNAi therapeutics. Tacere is located in San Jose, California, USA. For additional information, please visit www.tacerebio.com.
CONTACTS:
TACERE THERAPEUTICS, INC.
Mike Catelani
Chairman, President & CFO
+1 408 839-1818
SAN JOSE, Calif., Feb. 3, 2011 /PRNewswire/ -- Tacere Therapeutics, Inc., an RNA interference (RNAi)-based therapeutics company, announced today that it has reacquired the development and commercialization rights to its Hepatitis C Virus (HCV) compounds throughout Asia from its strategic partner, Tokyo-based Oncolys BioPharma Inc.
"We are very happy to have regained control of the Asian development and commercialization rights to our family of HCV compounds," said Sara Hall Renison, Chief Executive Officer of Tacere. Mike Catelani, Chairman, President and CFO, added, "With the continued promising development of our lead HCV compound in partnership with Pfizer, holder of the non-Asian worldwide development and commercialization rights, we believe that we are well-positioned to commence regulatory activities in Asia."
About Tacere's family of HCV compounds
Tacere's family of HCV compounds, are novel therapeutic products containing three separate RNAi elements targeted against the Hepatitis C virus itself and encapsidated in an adeno-associated virus (AAV) protein coat. AAV delivery methods have demonstrated clinical safety, and preclinical animal studies with TT-034, the lead compound in the family, have shown the ability to penetrate hepatocytes (the site of HCV replication) at high levels following a single intravenous administration. In preclinical animal studies, this "cocktail in one drug" monotherapy targeted and cleaved the Hepatitis C virus itself at three different sites simultaneously without toxicity.
About Tacere Therapeutics, Inc.
Tacere is an innovative biotechnology company focused on developing therapeutics to treat human diseases using its proprietary knowledge in the development of RNAi therapeutics. Tacere is located in San Jose, California, USA. For additional information, please visit www.tacerebio.com.
CONTACTS:
TACERE THERAPEUTICS, INC.
Mike Catelani
Chairman, President & CFO
+1 408 839-1818
Liver Transplant Updates and Information
I was a failure as a parent, I didn't offer up a plush organ for Christmas. Who knew? Instead my children received legos, teddy bears, PLAY-DOH, cookie monster and everything nintendo.
;
This parent had unrealistic expectations for all my children, from the day of conception I had visions of little doctors and lawyers and such. Well, maybe not a lawyer.
If I knew then, what I know now, each of my children would have been registered in an organ of the month club.
Starting with my favorite organ
.
.
The liver makes many of the body’s most vital chemicals, including cholesterol, bile, proteins and the clotting factors needed to stop bleeding. It also stores sugars, proteins, vitamins for use later. The liver also helps break down harmful substances and metabolize drugs. He works in detox! Say liver in Japanese: Kanzou!
Some parents; ME. May assume these plush organs could serve as an inspiration to children; MINE, for a career in medicine. Although, its highly unlikely that my kids would have felt inspired. They would have either put "little yellow liver" in the microwave or gave it to the dog next door.
.,.
These little stuffed organs are strange, or are they?
Maybe these toys could bring a smile to a child or adult as they recover from surgery, in particular liver transplant surgery. As I looked at these fluffy little critters, I began to think of the friends I met online, or in person, who needed a transplant. Although, I knew many more who needed one, then received one.
As of today, on this cold winter morning , according to(OPTN) there are 110,233 candidates who are waiting for a transplant.
.
What's the number of candidates waiting for a liver in the US ?
16,066
Hepatitis C is the leading indication for liver transplantation, with HCV diagnosed in about half of the patients who receive liver transplants each year in the United States.
Best Hospitals For Liver Transplantation
On (November 17, 2010) – HealthGrades made available to organ transplant patients a list of those hospitals with the best track record for survival and chances of receiving a donor organ. This information is available, free to the public, at HealthGrades.com and is intended to help patients in need of kidney, lung, heart or liver transplants.
HealthGrades Liver Transplant Excellence Award recognized 4 recipients out of 95 hospitals evaluated:
California Pacific Medical Center – Pacific
UCSF Medical Center
Cleveland Clinic
Saint Lukes Episcopal Hospital
UCSF Medical Center
Cleveland Clinic
Saint Lukes Episcopal Hospital
The ratings of individual hospitals, as well as the full methodology of the analysis, can be found at http://www.healthgrades.com/.
Finding Support
Two great places for online support are here and here; or most certainly at a local transplant center. At one of these support groups you can connect face to face. For me, I loved my friends online. They soon became my saving grace, I will never forget the friends that kept me sane, as I quickly felt my world would forever change; when I heard those words " You have Hepatitis C".
.If you’ve received an organ transplant or are in need of an organ transplant, there are organ transplantation support groups available to you and your family to help deal with the organ transplantation waiting process, preparation for the organ transplant, and adjusting to the new lifestyle after your organ transplant.
The status.com theStatus.com is a free web-based service. Patients and families can use the website to create a private, secure and confidential place to share information about a patient’s care and condition.
The Transplant Process
The process starts with the physician or specialist who will be providing your care. If it is determined you need a transplant you will be referred to a transplant center. With the referral in hand the appointment for an evaluation begins.
There are many different tests and consults that will be performed to determine if you are a suitable candidate for liver transplantation. Below is a list of some of the tests that will be ordered as part of your evaluation. Other tests or consults may be ordered based on the results of these tests.
Blood/Urine/Stool tests - Blood tests and specimen collection to help assess your overall physical condition.
Colonoscopy – A procedure to screen your colon.
Endoscopy- A procedure to screen your upper gastrointestinal tract.
Chest X-ray - The test assesses the size of your heart and any lung abnormalities
MRI or CT Scan of Abdomen - Examines the kidneys, liver, and gallbladder for the presence of cysts, stones, lesions, portal vein patency, ascites, and or other abnormalities.
TB Skin testing - A small amount of solution is injected under the skin on your forearm to determine if you have been exposed to tuberculosis.
Gynecological exam – All women will need a gynecological exam within the last year. Mammograms are also required for all women over age 40.
Pulmonary function studies - If you have a history of lung disease or tobacco use, your transplant work-up may include pulmonary (lung) function studies.
Cardiac tests – These tests will assess your heart function and will include an echocardiogram, and electrocardiogram (EKG or ECG). A stress test and a cardiac catheterization are done if indicated.
Physical examination (gives the doctor an overall picture of the patient’s condition).
Everyone is different; therefore, every evaluation will be tailored to evaluate specific patient’s needs.
Medical Review Board:
When your evaluation is complete, your case will be presented to the Medical Review Board (the MRB). The MRB consists of a multidisciplinary team of hepatologists, transplant surgeons, transplant coordinators, a dietician, social workers, financial counselor and consulting physicians. The purpose of the MRB is to discuss each evaluant case by case and to determine possible candidacy. Recommendations may be made by the MRB prior to making a final decision for transplant eligibility. All evaluants will be notified via certified mail and contacted by their assigned coordinator of the MRB outcomes and recommendations.
Significant or advanced cardiac, pulmonary, nervous system or other systemic diseases, except where dual organ transplants are being considered (i.e. liver/lung. liver/kidney, liver/heart)
Systemic infection
Hepatocellular carincoma with extrahepatic (outside the liver) spread or vascular involvement
Presence of malignancies outside the liver with the exception of special cases such as neuroendocrine tumors
Hepatocellular carincoma with extrahepatic (outside the liver) spread or vascular involvement
Presence of malignancies outside the liver with the exception of special cases such as neuroendocrine tumors
Acute severe hemodynamic compromise at the time of transplantation if accompanied by compromise or failure of one or more vital organs. Severe compromise is defined by the requirement of inotropic agents to maintain systolic blood pressure >90 mm Hg or pulmonary hypertension with a mean of >33 mm Hg
Active alcohol or drug abuse
History of behavior pattern or psychiatric illness considered likely to interfere significantly with compliance
Lack of sufficient social support to allow 24 hour care
History of behavior pattern or psychiatric illness considered likely to interfere significantly with compliance
Lack of sufficient social support to allow 24 hour care
Portal vein thrombosis
Patients with uncontrolled severe comorbid medical conditions
Obesity (BMI >40), which may result in technical or medical complications in the peri-operative and post operative periods
Patients with uncontrolled severe comorbid medical conditions
Obesity (BMI >40), which may result in technical or medical complications in the peri-operative and post operative periods
Is There A Waiting Period for Transplant?
If you are accepted for transplantation, you will be placed on a national computer list of active candidates waiting for a donor. Recipients are chosen according to a complex set of criteria, including MELD Score (Model for End Stage Liver Disease) blood type, and length of time on the waiting list. Recipients are chosen primarily on the basis of medical urgency within each ABO blood group. Waiting time is only a factor when patients have the same MELD score.
The United Network for Organ Sharing (UNOS) coordinates the equitable sharing of organs throughout the United States and oversees all donor centers and procurement agencies. MELD SCORE - is a numerical scale used for adult liver transplant candidates. The range is from 6 (less ill) to 40 (gravely ill). The individual score determines how urgently a patient needs a liver transplant. The number is calculated using your most recent laboratory tests. For additional information please log on to http://www.unos.org/ .
Lab values used in the MELD calculation:
Bilirubin, which measures how effectively the liver excretes bile;
INR (formally known as the prothrombin time), measures the liver’s ability to make blood clotting factors;
Creatinine, which measures kidney function. Impaired kidney function is often associated with severe liver disease.
INR (formally known as the prothrombin time), measures the liver’s ability to make blood clotting factors;
Creatinine, which measures kidney function. Impaired kidney function is often associated with severe liver disease.
.
Patient Services
UNOS’ Patient Services Department provides transplantation and donation information to patients, family members, friends, potential donors and medical professionals. Information can be requested on topics such as:
The transplantation and donation process
.
UNOS’ Patient Services Department provides transplantation and donation information to patients, family members, friends, potential donors and medical professionals. Information can be requested on topics such as:
The transplantation and donation process
.
Living donation
Various national, regional, state and center-specific data reports
Many other helpful resources are available:
Transplant Living >
Various national, regional, state and center-specific data reports
Many other helpful resources are available:
Transplant Living >
No matter where you are in the transplant experience, Transplant Living can help you be prepared with helpful information, resources and tools.
Patient Brochures >
Patient Brochures >
Find free information designed to help patients understand the organ transplant process. You can also request custom patient information packets here.
Fact Sheets >
Fact Sheets >
Review and print summary presentations of various topics relating to transplantation.
Check out the waiting list at your hospitial.
At the website (OPTN) =Organ Procurement and Transplantation Nework, the site offers a datasource listing each state in the U.S. where a patient can choose a hospitial and read a detailed profile of the current "Liver Waiting List" from the chosen center. This datasource allows the candidate to search according to; State, Age, Blood Type, Ethnicity, and Gender
Included is "Waiting List Data;
The candidate can choose to search for either or both A and B profiles.
Candidates need to pick either ; Registration or Candidate
Waiting List Data
A. Profile of current Liver Waiting List with recent additions and removals
Registrations - A patient who is waiting at more than one center, or for multiple organs, has multiple registrations.
Candidates - A patient who is waiting at more than one center, or for multiple organs, is considered as one candidate.
B. Profile of Percent Transplanted Liver Waiting List Registrations (Regional Data only)
In the "Transplant Data" section the candiate can search for any of the following;
In the "Transplant Data" section the candiate can search for any of the following;
C. Profile of Liver Transplants
D. Liver Transplants by Transplant Center within OPO service area
E. Profile of Graft Survival Rates for Liver Transplants (Regional Data only)
F. Profile of Patient Survival Rates for Liver Transplants (Regional Data only)
,
Donor Data
G. Profile of Deceased and Living Liver Donors by OPO service area.
G. Profile of Deceased and Living Liver Donors by OPO service area.
After entering your search criteria up pops the report.
.,
.Noted at the site; To find risk-adjusted, transplant-related statistics for specific transplant centers, please see the Scientific Registry of Transplant Recipients (SRTR) [Exit Disclaimer] Web site. The SRTR site contains data that enables patients to measure the performance of various transplant centers. The SRTR Web site is produced and maintained by the Chronic Disease Research Group of the Minneapolis Medical Research Foundation that holds the Scientific Registry of Transplant Recipients contract.
Hepatitis C Treatment and Liver Transplantation
,
In The News
,
Advances in Chronic Hepatitis C Treatment And Liver Transplantation: An Update
,
Jan 2011
The Center for the Study of Hepatitis C (CSHC) at NewYork-Presbyterian/Weill Cornell Medical Center is engaged in diverse HCV investigations.
One of us (Dr. Talal) has undertaken research on viral kinetics, presenting the first evaluation of pegIFN pharmacokinetics in patients coinfected with HCV and HIV, finding that, although pharmacokinetic parameters do not differentiate sustained virological responders from nonresponders, certain pharmaco - dynamic measurements do and might therefore serve as useful predictors of treatment outcome.
.
Free registration is required, I know ! Hate that.
By registering on our website, you will have access to all of McMahon Publishing's websites. Registration is free. Just fill in the form below and you're done!
.
Download to read this article in PDF document:
.
First liver transplant patients receive experimental drug to prevent hepatitis C infection
January 18, 2011 -->
"In nearly all cases, the patient's new liver is eventually infected by HCV because the virus remains in the patient's bloodstream during surgery. The course of recurrent HCV disease is accelerated after transplantation and up to 20 percent of transplant patients develop cirrhosis within five years. Unfortunately, the standard antiviral drugs currently used to treat HCV prior to the onset of end-stage liver disease are poorly tolerated after liver transplantation, leaving these patients"
;
The first patients were enrolled in the study in December. The primary goal of this randomized, double-blind, placebo-controlled study is to test if the monoclonal antibody, designated MBL-HCV1, prevents re-infection of patients chronically infected with HCV who are undergoing liver transplantation.
.
MassBiologics plans to enroll 16 patients in the first part of the study. "We are hopeful that positive results from this study will meet an important public health need, and we could not take this important step without the willing and thoughtful participation of these volunteers," said Donna Ambrosino, MD, executive director of MassBiologics and a professor of pediatrics at the Medical School.
There are currently five hospitals participating in the trial—Massachusetts General Hospital, Beth Israel Deaconess Medical Center, both in Boston, Lahey Clinic in Burlington, Massachusetts, Yale-New Haven Hospital in Connecticut and Mount Sinai Hospital in New York City—and others may join in the coming months. The first six patients enrolled have come from three of these sites.
.
HCV damages the liver and is the leading indication for liver transplantation, diagnosed in about half of the 6,000 patients who receive liver transplants each year in the United States. According to the US Centers for Disease Control and Prevention, 3.2 million Americans are chronically infected with HCV and approximately 10,000 die annually of the disease. Globally, as many as 170 million people are estimated to suffer from HCV infection.
For patients with end-stage liver disease from HCV infection, liver transplantation is the only option. While it can be a life-saving treatment, transplantation does not cure the disease. In nearly all cases, the patient's new liver is eventually infected by HCV because the virus remains in the patient's bloodstream during surgery. The course of recurrent HCV disease is accelerated after transplantation and up to 20 percent of transplant patients develop cirrhosis within five years. Unfortunately, the standard antiviral drugs currently used to treat HCV prior to the onset of end-stage liver disease are poorly tolerated after liver transplantation, leaving these patients
To address this unmet medical need, the team at MassBiologics, working in collaboration with investigators Gyongyi Szabo, MD, PhD, professor of medicine, and Robert Finberg, MD, professor and chair of the Department of Medicine at UMMS, set out to develop a human monoclonal antibody that could clear HCV from a patient's bloodstream and protect the donated liver from infection. In pre-clinical studies, MBL-HCV1 successfully neutralized the virus in cell culture and animal models of infection. A Phase 1 study in 31 healthy volunteers completed in 2009 showed the antibody was well tolerated, with no serious side effects. The Phase 1 study also measured the levels of the antibody in the bloodstream and its ability to bind and inactivate the virus, thereby helping to establish the dosage and protocol for the Phase 2 study now under way.
In the current study, patients will be randomized to receive an infusion of either the antibody or placebo between one and four hours prior to surgery. Then, during the phase of surgery when the diseased liver is removed, but before the donor liver is implanted, patients will receive a second infusion of either the antibody or placebo. After the surgery is completed, the patients will receive a third infusion, and then daily infusions during the first week of recovery. A final infusion is administered on the 14th day after liver transplantation.
"The liver is the main reservoir for the hepatitis C virus," said Brett Leav, MD, senior director of clinical affairs at MassBiologics. "The virus circulates in the blood, but only resides and replicates in the liver. So the idea here is to clear the virus from the bloodstream before it has an opportunity to re-infect the new liver."
After transplantation, patients' blood will be tested on a regular basis to screen for reemergence of HCV, which is usually detected within the first week after transplantation. The primary goal of the Phase 2 trial is to see if the patients who received the antibody are free of HCV at 42 days after transplantation. An interim analysis is planned after the first 16 patients have been enrolled in the trial, and a Data Safety and Monitoring Board overseeing the study will assess the effectiveness and safety of MBL-HCV1.
Vertex and Tibotec also plan to conduct several additional clinical trials of telaprevir in 2011 that aim to expand the future patient population for telaprevir-based regimens.
Phase 2 Post-Transplant Study: Vertex recently completed a drug-drug interaction study of telaprevir with immunosuppressive agents commonly used following a liver transplant. Based on results from this study, Vertex and Tibotec plan to initiate in 2011 a Phase 2 study of telaprevir-based regimens in people with recurrent hepatitis C following a liver transplant.
On This Blog; 2011
2010
Transplant Journals;
Transplant International
2011, Journal
Transplant Infectious Disease
2011, Journal
Clinical Transplantation
2011, Journal
Pediatric Transplantation
2011, Journal
2011, Journal
Transplant Infectious Disease
2011, Journal
Clinical Transplantation
2011, Journal
Pediatric Transplantation
2011, Journal
Evaluation of the Patient for Liver Transplantation
June 2005; Last reviewed 2008 September
Scheduled Update ; 2011
.
Upcoming Meeting
December 16-17, 2011, Lisbon, Portugal
Cancer; Analysis details Avastin's rare fatal side effects
Analysis details Avastin's rare fatal side effects
By CARLA K. JOHNSON AP Medical Writer
CHICAGO (AP) -- A new analysis raises fresh questions about the risks of the blockbuster cancer drug Avastin, suggesting the chance of dying from side effects linked to it is higher than the risk for patients on chemotherapy alone.
The drug's alarming problems - severe bleeding, holes in the bowel, problems with wound healing - are already known. The new review, based on an analysis of 16 studies and including more than 10,000 patients, quantifies the risk of death and clarifies how it cuts across different cancers.
Avastin was first approved for treating advanced colon cancer in 2004. Since then, it gradually gained federal approval for treating other advanced cancers, including breast, kidney and lung. Then in December, federal regulators began the process of withdrawing approval for its use as a breast cancer treatment.
The drug - which can cost up to $10,000 a month - is given to patients with advanced cancers, some of whom may be willing to take a chance to get a few more good months. But it's still unclear which patients are most likely to benefit from it, so the new findings underscore the complicated risk-benefit analysis that doctors must consider.
"It really points out how little we know," said Dr. Neil Spector of the Duke Cancer Institute in Durham, N.C., who wasn't involved in the study. "We need research to tell us who we can look in the face and say this drug warrants the potential risk."
Deaths from Avastin's side effects are rare and the small risk should be weighed against the drug's possible benefits, said senior study author Dr. Shenhong Wu of Stony Brook University Cancer Center in New York.
"Patients need to be aware of the risks when they consider their treatment options," said Wu. His research appears in Wednesday's Journal of the American Medical Association.
Charlotte Arnold, a spokeswoman for Avastin's maker, Genentech, said the new analysis is based on known information and includes studies in cancer types for which the drug isn't approved. She said the company supports research to find biomarkers that might reveal which patients may respond to Avastin. The company "takes patient safety very seriously," she said.
There was great hope for Avastin in the beginning. It was the first drug designed to slow tumors by blocking new blood vessels. It worked differently from chemotherapy and didn't cause hair loss or nausea. That may have encouraged some doctors to let their guard down, Spector said.
"We tend to look at it as a safer option, when, in fact, here's a drug that is unfortunately associated with fatal events," he said.
The Food and Drug Administration said Avastin should not be used to treat breast cancer after a research review suggested it failed to help those patients live longer or provide enough benefit to outweigh its risks.
It is still approved for advanced cancers of the colon, kidney, brain and lung. California-based Genentech, a unit of Swiss drugmaker Roche, is studying Avastin in other cancers. The company has appealed the FDA's decision on breast cancer, and some breast cancer patients are upset, saying they want the drug as an option.
The new analysis found 2.5 percent of patients on Avastin died from bleeding and other side effects thought to be caused by the drug. Fatal side effects were 1.5 times more frequent among patients on Avastin plus chemotherapy than among those getting chemotherapy alone.
The highest risk was seen in patients with prostate and lung cancer, the lowest in patients with kidney and breast cancer. The drug isn't approved for prostate cancer, but has been studied in those patients.
Overall, there were 148 deaths from side effects in 5,589 patients on Avastin and chemotherapy. There were 72 deaths from side effects in 4,628 patients on chemotherapy alone.
Just as the drug blocks new blood vessels that nourish tumors, it may also block new vessels that help the body heal and keep tissues strong. The findings highlight the importance of monitoring patients on Avastin for bleeding and other warning signs.
Experts have called on Genentech to do research to sort out which patients are most likely to benefit or be harmed by Avastin.
"That's an important part of clinical research," said Dr. Daniel Hayes, clinical director of the breast cancer program at the University of Michigan. Hayes wrote an accompanying editorial in the journal but wasn't involved in the analysis.
Avastin's enormous costs also must be considered, he said. The drug is dripped into a vein and must be given in a medical office or hospital.
"This drug is as expensive as any therapy we've ever had in cancer," he said. "We can't afford to give a drug to everybody when it helps only a portion of those to whom it is given."
Roche reported Avastin sales of nearly $6 billion in 2009.
---
Online:
JAMA: http://jama.ama-assn.org
© 2011 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
Learn more about our Privacy Policy and Terms of Use.
By CARLA K. JOHNSON AP Medical Writer
CHICAGO (AP) -- A new analysis raises fresh questions about the risks of the blockbuster cancer drug Avastin, suggesting the chance of dying from side effects linked to it is higher than the risk for patients on chemotherapy alone.
The drug's alarming problems - severe bleeding, holes in the bowel, problems with wound healing - are already known. The new review, based on an analysis of 16 studies and including more than 10,000 patients, quantifies the risk of death and clarifies how it cuts across different cancers.
Avastin was first approved for treating advanced colon cancer in 2004. Since then, it gradually gained federal approval for treating other advanced cancers, including breast, kidney and lung. Then in December, federal regulators began the process of withdrawing approval for its use as a breast cancer treatment.
The drug - which can cost up to $10,000 a month - is given to patients with advanced cancers, some of whom may be willing to take a chance to get a few more good months. But it's still unclear which patients are most likely to benefit from it, so the new findings underscore the complicated risk-benefit analysis that doctors must consider.
"It really points out how little we know," said Dr. Neil Spector of the Duke Cancer Institute in Durham, N.C., who wasn't involved in the study. "We need research to tell us who we can look in the face and say this drug warrants the potential risk."
Deaths from Avastin's side effects are rare and the small risk should be weighed against the drug's possible benefits, said senior study author Dr. Shenhong Wu of Stony Brook University Cancer Center in New York.
"Patients need to be aware of the risks when they consider their treatment options," said Wu. His research appears in Wednesday's Journal of the American Medical Association.
Charlotte Arnold, a spokeswoman for Avastin's maker, Genentech, said the new analysis is based on known information and includes studies in cancer types for which the drug isn't approved. She said the company supports research to find biomarkers that might reveal which patients may respond to Avastin. The company "takes patient safety very seriously," she said.
There was great hope for Avastin in the beginning. It was the first drug designed to slow tumors by blocking new blood vessels. It worked differently from chemotherapy and didn't cause hair loss or nausea. That may have encouraged some doctors to let their guard down, Spector said.
"We tend to look at it as a safer option, when, in fact, here's a drug that is unfortunately associated with fatal events," he said.
The Food and Drug Administration said Avastin should not be used to treat breast cancer after a research review suggested it failed to help those patients live longer or provide enough benefit to outweigh its risks.
It is still approved for advanced cancers of the colon, kidney, brain and lung. California-based Genentech, a unit of Swiss drugmaker Roche, is studying Avastin in other cancers. The company has appealed the FDA's decision on breast cancer, and some breast cancer patients are upset, saying they want the drug as an option.
The new analysis found 2.5 percent of patients on Avastin died from bleeding and other side effects thought to be caused by the drug. Fatal side effects were 1.5 times more frequent among patients on Avastin plus chemotherapy than among those getting chemotherapy alone.
The highest risk was seen in patients with prostate and lung cancer, the lowest in patients with kidney and breast cancer. The drug isn't approved for prostate cancer, but has been studied in those patients.
Overall, there were 148 deaths from side effects in 5,589 patients on Avastin and chemotherapy. There were 72 deaths from side effects in 4,628 patients on chemotherapy alone.
Just as the drug blocks new blood vessels that nourish tumors, it may also block new vessels that help the body heal and keep tissues strong. The findings highlight the importance of monitoring patients on Avastin for bleeding and other warning signs.
Experts have called on Genentech to do research to sort out which patients are most likely to benefit or be harmed by Avastin.
"That's an important part of clinical research," said Dr. Daniel Hayes, clinical director of the breast cancer program at the University of Michigan. Hayes wrote an accompanying editorial in the journal but wasn't involved in the analysis.
Avastin's enormous costs also must be considered, he said. The drug is dripped into a vein and must be given in a medical office or hospital.
"This drug is as expensive as any therapy we've ever had in cancer," he said. "We can't afford to give a drug to everybody when it helps only a portion of those to whom it is given."
Roche reported Avastin sales of nearly $6 billion in 2009.
---
Online:
JAMA: http://jama.ama-assn.org
© 2011 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
Learn more about our Privacy Policy and Terms of Use.
Researchers criticize AIDS spending, stigma
Researchers criticize AIDS spending, stigma
By DONNA BRYSON Associated Press
JOHANNESBURG (AP) -- Nearly 3 million lives have been saved by HIV/AIDS treatment but scarce resources are being misspent and stigma is still keeping the most vulnerable from seeking help, according to a new book by researchers commissioned by the U.N.
The failings are particularly worrying at a time when worldwide recession and donor fatigue are hurting spending on AIDS, the researchers say.
Among the two dozen people involved in the research was Nelson Mandela Foundation chief executive Achmat Dangor, who hosted a discussion of the research Thursday.
The book was aimed at ensuring that "the response to AIDS is systematic and effective in the long term," Dangor said. "We believe it is crucial also to our founder's legacy."
Since finishing his term as South Africa's first black president, Mandela has campaigned to raise awareness about AIDS in the country with the world's largest AIDS burden. Now 92 and ailing, the anti-apartheid icon galvanized the AIDS community in 2005 when he publicly acknowledged the disease killed his son.
The researchers were asked by the U.N. AIDS agency three years ago to review how the world has tackled the disease. The experts also were asked to determine what changes need to be made to radically reduce the number of infections and deaths by 2031, which will mark 50 years since the AIDS virus was first reported.
The researchers, collectively known as the aids2031 Consortium, said it was "fair to ask whether the AIDS effort has always achieved good value for its money."
"Despite a more than 53-fold increase in AIDS funding in barely over a decade, the epidemic continues to outpace the rate at which programs are delivering," they said in the book entitled "AIDS: Taking a Long-Term View."
The researchers said developing treatments and getting the drugs to the infected saved nearly 3 million lives between 1996 and 2008. Efforts to prevent infected mothers from transmitting HIV to their babies averted at least 200,000 new infections around the world between 1996 and 2008.
But every day, more than 7,000 people become infected, more than twice as many as are able to start AIDS treatment.
The researchers called for a new focus on prevention, and criticized governments for ignoring research that could help guide efforts. For example, programs in Uganda focused on young people while research has shown high rates of HIV among older adults in steady relationships in the East African country.
Laws making homosexual sex a crime and harassment of intravenous drug users also keep those who need it most from seeking help, the researchers said.
Changing society's attitudes is a long-term project, without the quick, measurable results of increasing the spread of AIDS treatment drugs, the researchers acknowledged. They said the costs of a lifetime of treatment for millions of HIV-infected people in poor countries is unsustainable.
After Dr. Aaron Motsoaledi took over as South Africa's health minister in 2009, he said he was baffled by how much the government was spending to buy AIDS drugs from private companies. South Africa, the country with the most people living with HIV in the world, provides free AIDS treatment to its citizens.
Late last year, Motsoaledi announced that by taking such steps as asking more companies to bid and demanding they provide costs breakdowns, he had cut costs by more than half.
The Global Fund to Fight AIDS, Tuberculosis and Malaria, which endorsed aids2031's work, also has found that up to two-thirds of some grants it provides are lost to corruption. The independent agency, backed by celebrity campaigners, is a major international funder of AIDS programs.
© 2011 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed. Learn more about our Privacy Policy and Terms of Use.
By DONNA BRYSON Associated Press
JOHANNESBURG (AP) -- Nearly 3 million lives have been saved by HIV/AIDS treatment but scarce resources are being misspent and stigma is still keeping the most vulnerable from seeking help, according to a new book by researchers commissioned by the U.N.
The failings are particularly worrying at a time when worldwide recession and donor fatigue are hurting spending on AIDS, the researchers say.
Among the two dozen people involved in the research was Nelson Mandela Foundation chief executive Achmat Dangor, who hosted a discussion of the research Thursday.
The book was aimed at ensuring that "the response to AIDS is systematic and effective in the long term," Dangor said. "We believe it is crucial also to our founder's legacy."
Since finishing his term as South Africa's first black president, Mandela has campaigned to raise awareness about AIDS in the country with the world's largest AIDS burden. Now 92 and ailing, the anti-apartheid icon galvanized the AIDS community in 2005 when he publicly acknowledged the disease killed his son.
The researchers were asked by the U.N. AIDS agency three years ago to review how the world has tackled the disease. The experts also were asked to determine what changes need to be made to radically reduce the number of infections and deaths by 2031, which will mark 50 years since the AIDS virus was first reported.
The researchers, collectively known as the aids2031 Consortium, said it was "fair to ask whether the AIDS effort has always achieved good value for its money."
"Despite a more than 53-fold increase in AIDS funding in barely over a decade, the epidemic continues to outpace the rate at which programs are delivering," they said in the book entitled "AIDS: Taking a Long-Term View."
The researchers said developing treatments and getting the drugs to the infected saved nearly 3 million lives between 1996 and 2008. Efforts to prevent infected mothers from transmitting HIV to their babies averted at least 200,000 new infections around the world between 1996 and 2008.
But every day, more than 7,000 people become infected, more than twice as many as are able to start AIDS treatment.
The researchers called for a new focus on prevention, and criticized governments for ignoring research that could help guide efforts. For example, programs in Uganda focused on young people while research has shown high rates of HIV among older adults in steady relationships in the East African country.
Laws making homosexual sex a crime and harassment of intravenous drug users also keep those who need it most from seeking help, the researchers said.
Changing society's attitudes is a long-term project, without the quick, measurable results of increasing the spread of AIDS treatment drugs, the researchers acknowledged. They said the costs of a lifetime of treatment for millions of HIV-infected people in poor countries is unsustainable.
After Dr. Aaron Motsoaledi took over as South Africa's health minister in 2009, he said he was baffled by how much the government was spending to buy AIDS drugs from private companies. South Africa, the country with the most people living with HIV in the world, provides free AIDS treatment to its citizens.
Late last year, Motsoaledi announced that by taking such steps as asking more companies to bid and demanding they provide costs breakdowns, he had cut costs by more than half.
The Global Fund to Fight AIDS, Tuberculosis and Malaria, which endorsed aids2031's work, also has found that up to two-thirds of some grants it provides are lost to corruption. The independent agency, backed by celebrity campaigners, is a major international funder of AIDS programs.
© 2011 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed. Learn more about our Privacy Policy and Terms of Use.
Protease Inhibitor–Resistant Hepatitis C Virus Mutants With Reduced Fitness From Impaired Production of Infectious Virus
GastroenterologyVolume 140, Issue 2 , Pages 667-675, February 2011
Protease Inhibitor–Resistant Hepatitis C Virus Mutants With Reduced Fitness From Impaired Production of Infectious Virus
Background & Aims
Several small molecule inhibitors of the hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease have advanced successfully to clinical trials. However, the selection of drug-resistant mutants is a significant issue with protease inhibitors (PIs). A variety of amino acid substitutions in the protease domain of NS3 can lead to PI resistance. Many of these significantly impair the replication fitness of HCV RNA replicons. However, it is not known whether these mutations also adversely affect infectious virus assembly and release, processes in which NS3 also participates.
Methods
We studied the impact of 25 previously identified PI-resistance mutations on the capacity of genotype 1a H77S RNA to replicate in cell culture and produce infectious virus.
Results
Most PI-resistance mutations resulted in moderate loss of replication competence, although several (V36A/L/M, R109K, and D168E) showed fitness comparable to wild type, whereas others (S138T and A156V) were severely impaired both in RNA replication and infectious virus production. Although reductions in RNA replication capacity correlated with decreased yields of infectious virus for most mutations, a subset of mutants (Q41R, F43S, R155T, A156S, and I170A/T) showed greater impairment in their ability to produce virus than predicted from reductions in RNA replication capacity. Detailed examination of the I170A mutant showed no defect in release of virus from cells and no significant difference in specific infectivity of extracellular virus particles.
Conclusions
Replicon-based assays might underestimate the loss of fitness caused by PI-resistance mutations, because some mutations in the NS3 protease domain specifically impair late steps in the viral life cycle that involve intracellular assembly of infectious virus.
Tetsuro Shimakami
Affiliations Division of Infectious Diseases, Department of Medicine, Inflammatory Diseases Institute, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, Christoph Welsch
Affiliations Division of Infectious Diseases, Department of Medicine, Inflammatory Diseases Institute, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Department of Internal Medicine, Johann Wolfgang Goethe-University, Frankfurt, Germany Max Planck Institute for Informatics, Computational Biology, and Applied Algorithmics, Saarbrücken, Germany, Daisuke Yamane
Affiliations Division of Infectious Diseases, Department of Medicine, Inflammatory Diseases Institute, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, David R. McGivern
Affiliations Division of Infectious Diseases, Department of Medicine, Inflammatory Diseases Institute, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, MinKyung Yi
Affiliations Institute for Human Infections & Immunity and Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, Stefan Zeuzem
Affiliations Department of Internal Medicine, Johann Wolfgang Goethe-University, Frankfurt, Germany, Stanley M. Lemon
Affiliations
Division of Infectious Diseases, Department of Medicine, Inflammatory Diseases Institute, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Reprint requests Address requests for reprints to: Stanley M. Lemon, MD, Inflammatory Diseases Institute CB#7292, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7292. fax (919) 843-7240 Received 11 June 2010; accepted 28 October 2010. published online 08 November 2010. Abstract
Protease Inhibitor–Resistant Hepatitis C Virus Mutants With Reduced Fitness From Impaired Production of Infectious Virus
Background & Aims
Several small molecule inhibitors of the hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease have advanced successfully to clinical trials. However, the selection of drug-resistant mutants is a significant issue with protease inhibitors (PIs). A variety of amino acid substitutions in the protease domain of NS3 can lead to PI resistance. Many of these significantly impair the replication fitness of HCV RNA replicons. However, it is not known whether these mutations also adversely affect infectious virus assembly and release, processes in which NS3 also participates.
Methods
We studied the impact of 25 previously identified PI-resistance mutations on the capacity of genotype 1a H77S RNA to replicate in cell culture and produce infectious virus.
Results
Most PI-resistance mutations resulted in moderate loss of replication competence, although several (V36A/L/M, R109K, and D168E) showed fitness comparable to wild type, whereas others (S138T and A156V) were severely impaired both in RNA replication and infectious virus production. Although reductions in RNA replication capacity correlated with decreased yields of infectious virus for most mutations, a subset of mutants (Q41R, F43S, R155T, A156S, and I170A/T) showed greater impairment in their ability to produce virus than predicted from reductions in RNA replication capacity. Detailed examination of the I170A mutant showed no defect in release of virus from cells and no significant difference in specific infectivity of extracellular virus particles.
Conclusions
Replicon-based assays might underestimate the loss of fitness caused by PI-resistance mutations, because some mutations in the NS3 protease domain specifically impair late steps in the viral life cycle that involve intracellular assembly of infectious virus.
Tetsuro Shimakami
Affiliations Division of Infectious Diseases, Department of Medicine, Inflammatory Diseases Institute, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, Christoph Welsch
Affiliations Division of Infectious Diseases, Department of Medicine, Inflammatory Diseases Institute, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Department of Internal Medicine, Johann Wolfgang Goethe-University, Frankfurt, Germany Max Planck Institute for Informatics, Computational Biology, and Applied Algorithmics, Saarbrücken, Germany, Daisuke Yamane
Affiliations Division of Infectious Diseases, Department of Medicine, Inflammatory Diseases Institute, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, David R. McGivern
Affiliations Division of Infectious Diseases, Department of Medicine, Inflammatory Diseases Institute, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, MinKyung Yi
Affiliations Institute for Human Infections & Immunity and Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, Texas, Stefan Zeuzem
Affiliations Department of Internal Medicine, Johann Wolfgang Goethe-University, Frankfurt, Germany, Stanley M. Lemon
Affiliations
Division of Infectious Diseases, Department of Medicine, Inflammatory Diseases Institute, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Reprint requests Address requests for reprints to: Stanley M. Lemon, MD, Inflammatory Diseases Institute CB#7292, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7292. fax (919) 843-7240 Received 11 June 2010; accepted 28 October 2010. published online 08 November 2010. Abstract
Update;MELD score and Liver Transplant
The MELD Score and Liver Transplant: An Update for Patients 
Patients awaiting transplant commonly have questions regarding there MELD score, and how this number is determined. As you can imagine, there is great anxiety in patients awaiting transplant. At almost every clinic visit, patients are asking for they’re updated score. In my own practice, at every visit we calculate the new score and discussed this result with them. The MELD score, which we have been using for the past several years, is calculated by taking the patient’s most recent bilirubin, creatinine, and INR, which is then entered into the computer and calculated. Theoretically, the MELD score can arrange in values between 5 and 40. It has generally been accepted that patients with a MELD score less than 15 have a better survival is not transplanted. Those with scores over 15 should be considered for transplant.
The higher the MELD score, the more ill the patient is, with a greater likelihood of not surviving. In the greater Houston area, most of the transplant programs, including ours at the Methodist Hospital, are transplanting patients with MELD score is greater than 25.
There are certain exceptions to the MELD score. Many of these are developed regionally. With patients who develop hepatocellular carcinoma, in most cases, they will receive a MELD exception of 22 points, even if they have a lower calculated score as described above. It’s been well established that patients with liver cancer should be transplanted quickly. This MELD exception allows this to take place.
If after 3 months the patient is not transplanted, additional points are granted. Other MELD exceptions for pulmonary hypertension, refractory gastrointestinal bleeding, and refractory ascites are also allowed. These are given on a case by case basis after a regional review by other transplant centers. Not every exception is granted, and this could be another source of anxiety for patients and their family.
Looking at the bilirubin, creatinine, and INR, you could see that as the patient becomes more ill, their MELD score will reflect a higher value.
Looking at the bilirubin, creatinine, and INR, you could see that as the patient becomes more ill, their MELD score will reflect a higher value.
It is very difficult to sit with the patient who has a low MELD score, who happens to feel very ill, and tells him that they must continue to get even more debilitated before a transplant is performed. While the current allocations system works for the vast majority of patients, there are always going to be those patients that have a MELD score that does not accurately represent how sick they are. For these patients, this is where most of the anxiety and concern is present. The best that we can do as physicians and other healthcare providers is to reassure them and worked very closely with them. I personally have been involved in liver transplantation for over 20 years, and the same issues we faced 20 years ago, despite a different allocations system, remained today.
To calculate your own MELD score, I have listed a link below. Of course, if you have any questions, feel free to contact me or post your comments on this blog for others to see and learn from. You can always reach me at Liver Specialists of Texas at 713-794-07 00.
Calculate your MELD score here.
Calculate your MELD score here.
Study raises questions over 'adult' stem cells
Study raises questions over 'adult' stem cells
(AFP) –
Feb 03
11 hours ago
PARIS — The quest to generate replacement tissue in the lab faced questions on Thursday over mature cells whose DNA is "reprogrammed" so that they grow with youthful vigour into new cells.
Cellular reprogramming last year emerged as the new frontier in the heavily promoted search to grow cells to replenish heart, liver, muscle or other tissue damaged by disease, age or accident.In 2010, scientists announced they had been able to wipe out the DNA programming of mature (also called adult) cells, yielding versatile stem cells that would be the raw material for organ-specific cells.
That announcement sparked great excitement.These reverse-engineered cells seemed to look and act as an alternative to stem cells from human embryos -- a miraculously potent but controversial and limited source.But the new study, published in Nature on Thursday, suggests the hoped-for substitute, induced pluripotent stem cells (iPSCs), does not become a completely blank slate, as thought.Instead, peripheral parts of their code are riddled with indelible marks, "a consistent pattern of reprogramming errors," its authors said.
"Embryonic stem cells are considered the gold standard for pluripotency," said lead researcher Joseph Ecker of the Salk Institute for Biological Studies in La Jolla, California, referring to the ability of stem cells to form different types of cells found in the body."So we need to know whether -- and if so, how -- iPSCs differ from embryonic cells."The researchers found that the transformation from adult to stem cell was invariably incomplete or inadequate, leaving telltale "hotspots" in the DNA code.
Moreover, these reprogramming quirks were passed on when iPSCs were then coaxed into a more specialised cell type.
The signatures are not found at the core level of the gene, but in a peripheral zone called the epigenome. This is essentially the switching system that turns genes on or off and determines their level of activity.
In the study, researchers scrutinized well-known epigenetic elements called methylomes, comparing embryonic stems cells and iPSCs.At first glance, the patterns were nearly identical."But when we started to dig deeper, we discovered significant differences," said Ryan Lister, also at the Salk Institute.
The experiments revealed that the newly-generated stem cells maintained traces of their origins. An iPSC derived from a fat cell, for example, still showed residual signature patterns in its methylation.
Moreover, regardless of their origins, the iPSCs all showed that a region of DNA called telomeres and centromeres proved resistant to reprogramming.Telomeres are protective "caps" on the end of chromosomes, and play a key role in ageing and longevity. Centromeres, found near the axis of a chromosome, are involved in cell division.The new work added to previous research that shows iPSCs are indeed different from embyronic stem cells.
It did not explore, though, whether the "hotspots" hamper the cell's ability to replicate or become a new cell type, which are questions of vital importance.
"We can tell by looking at these hotspots whether a cell is an IPS cell or an embryonic stem cell," said Ecker. "But we don't know yet what it means for their self-renewal or differentiation potential."
Copyright © 2011 AFP. All rights reserved.
More »
(AFP) –
Feb 03
11 hours ago
PARIS — The quest to generate replacement tissue in the lab faced questions on Thursday over mature cells whose DNA is "reprogrammed" so that they grow with youthful vigour into new cells.
Cellular reprogramming last year emerged as the new frontier in the heavily promoted search to grow cells to replenish heart, liver, muscle or other tissue damaged by disease, age or accident.In 2010, scientists announced they had been able to wipe out the DNA programming of mature (also called adult) cells, yielding versatile stem cells that would be the raw material for organ-specific cells.
That announcement sparked great excitement.These reverse-engineered cells seemed to look and act as an alternative to stem cells from human embryos -- a miraculously potent but controversial and limited source.But the new study, published in Nature on Thursday, suggests the hoped-for substitute, induced pluripotent stem cells (iPSCs), does not become a completely blank slate, as thought.Instead, peripheral parts of their code are riddled with indelible marks, "a consistent pattern of reprogramming errors," its authors said.
"Embryonic stem cells are considered the gold standard for pluripotency," said lead researcher Joseph Ecker of the Salk Institute for Biological Studies in La Jolla, California, referring to the ability of stem cells to form different types of cells found in the body."So we need to know whether -- and if so, how -- iPSCs differ from embryonic cells."The researchers found that the transformation from adult to stem cell was invariably incomplete or inadequate, leaving telltale "hotspots" in the DNA code.
Moreover, these reprogramming quirks were passed on when iPSCs were then coaxed into a more specialised cell type.
The signatures are not found at the core level of the gene, but in a peripheral zone called the epigenome. This is essentially the switching system that turns genes on or off and determines their level of activity.
In the study, researchers scrutinized well-known epigenetic elements called methylomes, comparing embryonic stems cells and iPSCs.At first glance, the patterns were nearly identical."But when we started to dig deeper, we discovered significant differences," said Ryan Lister, also at the Salk Institute.
The experiments revealed that the newly-generated stem cells maintained traces of their origins. An iPSC derived from a fat cell, for example, still showed residual signature patterns in its methylation.
Moreover, regardless of their origins, the iPSCs all showed that a region of DNA called telomeres and centromeres proved resistant to reprogramming.Telomeres are protective "caps" on the end of chromosomes, and play a key role in ageing and longevity. Centromeres, found near the axis of a chromosome, are involved in cell division.The new work added to previous research that shows iPSCs are indeed different from embyronic stem cells.
It did not explore, though, whether the "hotspots" hamper the cell's ability to replicate or become a new cell type, which are questions of vital importance.
"We can tell by looking at these hotspots whether a cell is an IPS cell or an embryonic stem cell," said Ecker. "But we don't know yet what it means for their self-renewal or differentiation potential."
Copyright © 2011 AFP. All rights reserved.
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