find tumor cells can be killed by manipulating necrosis pathway
Last Updated: May 14, 2004
NEW YORK (Reuters Health) - Chemotherapy agents can kill by manipulating necrosis pathways as well as by inducing apoptosis, according to a new study that suggests that necrosis could be an important process by which new chemotherapeutic agents would work.
Many anti-cancer drugs work by inducing cell apoptosis, Dr. Craig B. Thompson and colleagues explain in the early online issue of Genes and Development for June 1. Unfortunately, most cancers develop mutations in apoptosis effectors, such as p53, Bax, Bak and caspases, and thus become resistant to apoptosis.
Because alkylating agents often remain effective despite loss of apoptotic induction, Dr. Thompson, at the University of Pennsylvania in Philadelphia, and his associates studied the effect of chemotherapeutic drugs on mouse embryo fibroblasts deficient in p53 or in Bax and Bak.
The two cell lines were as sensitive as wild-type cells to the alkylating agents nitrogen mustard and N-methyl-N-nitro-N-nitrosaguanidine (MNNG), but were resistant to the DNA topoisomerase inhibitor etoposide. The researchers found that alkylation activates poly(ADP-ribose) polymerase (PARP), which in turn leads to necrotic death and a pro-inflammatory response.
ATP production is maintained in proliferating cells almost exclusively through aerobic glycolysis, that is, the dual mechanisms of glycolysis and oxidative phosphorylation, the authors note. In contrast, nonproliferating cells utilize additional metabolic pathways to maintain energy production.
Necrosis, unlike apoptosis, induces an inflammatory response to the dying cells, thus perhaps contributing to the efficacy of chemotherapy drugs.
"It will be of interest to determine whether tumors resistant to DNA alkylating agents have acquired loss of or altered PARP activity," Dr. Thompson's group suggests.
Effective cancer treatment will likely require combination treatments that induce both apoptosis and necrosis, Drs. Deirdre A. Nelson and Eileen White comment in an accompanying editorial.
"Together with individual tumor typing and matching with type-specific treatments, (combinatorial approaches) will allow the goal of effective tumor-specific therapeutics, or personalized medicine," the editorialists write.
Sets New Rules on Tissue Donation
By LAURAN NEERGAARD
.c The Associated Press
WASHINGTON (AP) - People who donate sperm, eggs and other commonly transplanted tissues will have to be screened for infectious diseases like blood donors are, under long-awaited federal rules announced Thursday.
Donated blood and organs have been strictly regulated for a long time. But less subject to oversight are other donated tissue such as skin for burn victims, ligaments for knee surgery, umbilical cord blood, and sperm and eggs.
Human tissues can carry diseases. So the way cells are handled can make the difference between a therapy that works or one that is wasted or, worse, dangerous when the cells die or are contaminated.
In 2002, a 23-year-old Minnesota man died after knee reconstruction surgery that used bacteria-laden cartilage.
The Food and Drug Administration had proposed new regulations in 1997 designed to prevent such contamination.
The agency on Thursday finalized one long-delayed but important part of those rules: Who is eligible to donate.
Before the use of most tissue or cell types, tissue banks must ask a living donor or relatives of a dead one about risk factors for infections, a practice similar to the screening that blood banks now perform.
That means, for example, that anyone who has used injected drugs in the past five years or men who have had sex with another man in the preceding five years could not donate sperm or any other tissue. Those are risk factors for the AIDS virus.
In addition to screening, tissue banks must test donors and/or the donated tissue for diseases that include HIV, hepatitis B and C, syphilis and Creutzfeldt-Jakob disease, the human form of mad cow disease.
The FDA said additional testing will be required for some tissue donations, such as the sexually transmitted diseases chlamydia and gonorrhea for reproductive tissue. The rules allow the agency to order checks for new diseases, such as West Nile virus or SARS, as it deems necessary.
Exceptions include cells or tissue removed from the patient and transplanted back into that person, or reproductive cells from a sexual partner, as is common with in vitro fertilization.
thought Phase III
took longer than this. PR today.
BOSTON (Dow Jones)-- Boston Life Sciences Inc. (BLSI, news) began patient enrollment in its Phase III trial of Altropane, a radioimaging agent for the differentiation of Parkinsonian tremors from tremors due to other, non- Parkinsonian causes.
In a press release Thursday, Boston Life said the trial will enroll about 500 subjects and be completed in about 12 months.
The trial is being carried out under a binding agreement with the Food and Drug Admnistration regarding the protocol design. Boston Life and the FDA reached an agreement over the protocol design in April following eight months of talks.
A successful trial -- one that meets the endpoints, raises no safety concerns and complies with the protocol design -- will form the basis for the filing of a New Drug Application and the potential approvability of Altropane, the biotechnology company said.
(Voluntary Disclosure: Position- Long)
like to thank everyone posting today for making it easier for me to
bypass EVERY message posted by simply looking at ONLY the headers in the
Not a single post that had anything to do with the company.
Keep it up, idiots
Drugs Raise Risk of Artery Plaques
Friday, May 14, 2004
NEW YORK (Reuters Health) - Findings from an Italian study provide further evidence that HIV drugs called protease inhibitors may increase the risk of artery "plaques".
Because these drugs have been shown to markedly improve the survival of HIV-infected patients, the authors do not recommend simply abandoning them. Rather, patients treated with the drugs should undergo periodic ultrasound tests to look for these plaques. If these tests show worsening of the plaque then a treatment regimen that doesn't include these drugs may be warranted.
Dr. Paolo Maggi from University of Bari and colleagues used ultrasound to evaluate the association between anti-HIV drugs and artery plaques in a total of 293 HIV-infected patients. Specifically, they looked for plaques in a blood vessel in the neck called the carotid artery. The findings are reported in the medical journal AIDS.
One hundred five patients were treated with regimens that included protease inhibitors. The remaining patients were either treated with regimens that didn't include protease inhibitors or with nothing at all.
On follow-up, 52 percent of patients treated with protease inhibitors displayed plaques on ultrasound. In contrast, the rate among other patients was only about 15 percent. Age, smoking, and immune status all seemed to influence the risk of plaques, but the strongest predictor was the use of protease inhibitors, the authors note.
These findings support previous research by the same investigators reported in 2000.
Protease inhibitor regimens appear to be "major" players in the development of artery plaques, the authors conclude. Additional studies, they say, are needed to clarify exactly how such drugs may cause plaques.
SOURCE: AIDS, April 30, 2004.