Experimental Pill Fights Inherited Cancer

For the second time this month, researchers report success using a novel type of anticancer pill to curb the growth of inherited tumors that often defy standard treatment. Called olaparib, the experimental pill is a member of a new class of drugs called PARP inhibitors that prevent unstable cancer cells from repairing themselves.

Two-thirds of 19 patients with cancer caused by mutations in the BRCA1 or BRCA2 genes responded to treatment with olaparib, and in more than half, tumors shrank or stopped growing, says researcher Johann de Bono, MD, PhD, of the Institute of Cancer Research in Sutton, U.K.

Defects in the BRCA1 and BRCA2 genes place women at sharply increased risk of developing aggressive cancers of the breast and ovaries at a young age. BRCA2 gene mutations also raise a man's risk of prostate cancer.

Of 19 patients in the study with BRCA-inherited cancers, 15 had ovarian cancer, three had breast cancer, and one had prostate cancer.

Olaparib did not help 41 other patients with tumors that were not associated with BRCA mutations, de Bono says.

PARP inhibitors "will very likely change the way we treat patients" whose tumors are caused by BRCA defects, says Daniel Silver, MD, PhD, of the Dana-Farber Cancer Institute in Boston. Silver, who was not involved with the work, co-authored an editorial about the study.

The study appears in the June 25 issue of The New England Journal of Medicine.

PARP Inhibitors for Cancer: How They Work
PARP is short for poly (ADP-ribose) polymerase, an enzyme used by cancer cells to repair DNA damage.
All cells, cancerous and healthy alike, have multiple systems for DNA repair. Even if one pathway is turned off, most cells can survive.

In people with BRCA mutations, one pathway is shut down, much like a table that is missing one leg. The table can still stand on three legs, but it's unstable.

Along comes olaparib, knocking out the PARP pathway. Like a table that only has two legs left, the cancer cell falls over and dies, de Bono says.

Like other targeted therapies -- smart drugs that take aim at the nuts and bolts of tumor growth while leaving healthy tissue relatively unscathed -- PARP inhibitors cause fewer side effects than traditional chemotherapy, he tells WebMD. The most common side effects in the study were low-grade fatigue and mild stomach upset.

"My prostate cancer patient, who had advanced cancer that had spread to the bone, has been taking olaparib for two-and-one-half years. The drug is really active, and the only side effect is indigestion," de Bono says.

Another advantage of olaparib is that it's a pill that only has to be swallowed twice a day, he says.

PARP Inhibitors Targets Other Cancers, Too

PARP inhibitors will likely prove beneficial for other cancers, too, Silver tells WebMD.

In fact, they are already being tested in women with so-called triple-negative breast cancer. Such tumors are hard to treat because they lack receptors for the hormones estrogen and progesterone as well as the protein HER2, which are targeted by current therapies.

The hope is that eventually PARP inhibitors could be used at an early stage to treat or even prevent cancer in high-risk persons, Silver says.

Maker AstraZeneca, which helped to fund the work, plans to continue studying the drug, according to James Carmichael, MD, global medical director for olaparib. By Charlene Laino
WebMD Health News
Source: Google Health News

Artificial Heart’s Use Marks Milestone

Commercial implant is a first for Abiomed's self-contained device A self-contained artificial heart made by Abiomed Inc., a Danvers cardiac device company, has been successfully implanted in a patient at Robert Wood Johnson University Hospital in New Brunswick, N.J., marking the first commercial implantation of the device.

An earlier version of the device, called AbioCor, was implanted in 14 patients during clinical trials earlier this decade. But the latest procedure, which took place on June 15 and was disclosed by the hospital only yesterday, is the first since the company won Food and Drug Administration approval in 2006 to market AbioCor to heart patients who don’t qualify for transplants.

"It’s a great milestone for the company," Michael R. Minogue, chief executive of Abiomed, said yesterday.

Minogue acknowledged, however, that AbioCor is less likely to be a driver of the company’s revenue in the short term than a symbol of its technological know-how. Technology developed for the plastic-and-titanium replacement heart also has been used in some of Abiomed’s catheter-based heart pumps, which were approved by the FDA over the past year and are projected to serve much larger markets than AbioCor. "This is a specialty product," Minogue said of the device. "It’s a sign of our technology expertise. No other company makes a completely self-contained implantable artificial heart. But what we’re really focused on is heart recovery and helping people support the heart."

AbioCor is considered self-contained because it has a built-in battery, unlike earlier artificial hearts such as the Jarvik (now called CardioWest), which are tethered to external consoles. It also contains a microprocessor that sends radio signals to a computer monitoring the patient’s health.

The device is not designed to keep a patient alive indefinitely, but to extend the lives of dying patients who are too sick to receive transplants.

In addition to Robert Wood Johnson University Hospital, a teaching hospital affiliated with the University of Medicine and Dentistry of New Jersey, two other hospitals have been approved and trained by Abiomed to implant AbioCor: Johns Hopkins Hospital in Baltimore and St. Vincent Indianapolis Hospital.

The procedure costs $250,000, more than twice as much as a heart transplant, but the price is expected to come down over time.

Dr. Mark B. Anderson, the chief of cardiac surgery at Robert Wood Johnson Hospital who implanted the AbioCor last week, said the patient was a 76-year-old man with congestive heart failure who had previous bypass operations and did not qualify for a transplant.

Hospital officials declined to identify the patient, citing privacy concerns.

"We’re happy to report that the device is working very well and the patient is doing very well, Anderson said yesterday.

Abiomed has made improvements to the software and some of the hardware in AbioCor since the clinical trials. Those tests involved patients whose life expectancy would have been only a few days without the implantation, and at least one of them lived almost two years after receiving the artificial heart. With recent enhancements and a broader class of patients, the prognosis is now much better, Anderson said.

He said the number of implantations will increase and, as the technology improves over the coming decade, artificial hearts may come to rival transplanted human organs.

"Given the demographics of heart failure, there is the potential for a great number of these implantations," Anderson said. "I don’t want to suggest that we start putting the device in everyone, because transplants are a very good outcome."

Minogue said he announced the successful AbioCor implantation at a staff meeting in Danvers yesterday. Employees will celebrate at a summer outing in August. The 27-year-old company has about 340 employees worldwide, more than half of them working at its Danvers headquarters.

Click here for Interactive Diagram of the AbioCor Replacement Heart

Shares of Abiomed edged up 16 cents, or 1.9 percent, to $8.36 yesterday.

Robert Weisman can be reached at weisman@globe.com.

© Copyright 2009 Globe Newspaper Company.

Source: Google Health News

Cooking Carrots Whole Preserves More Anti-Cancer Properties, Study

A new study by UK scientists showed that cooking carrots whole preserves their anti-cancer properties better than cooking them sliced or diced.

The study was the work Dr Kirsten Brandt and researcher Ahlam Rashed at the University of Newcastle Upon Tyne and is being presented today at the NutrEvent nutrition and health conference that is taking place in Lille, France.Brandt and colleagues found that carrots boiled before cutting had 25 per cent more of the anti-cancer chemical falcarinol than those that were cut up before boiling.

They also found uncut cooked carrots had higher concentrations of the naturally occurring sugars that give them their distinctive flavour.

Brandt, who is based at the School of Agriculture, Food and Rural Development and the Human Nutrition Research Centre at Newcastle University said that:

Chopping up your carrots increases the surface area so more of the nutrients leach out into the water while they are being cooked.

By cooking them whole and chopping them up afterwards you are locking in both taste andnutrients so the carrot is better for you all round," she added.Working with colleagues at the University of Southern Denmark, Brandt and her team at Newcastle discovered the health properites of falcarinol in carrots four years ago.

They showed that feeding rats a diet containing either raw carrots or isolated falcarinol reduced their risk of developing tumors by one third compared with rats in a control group.

Since then the researchers have been looking at the health benefits of raw and cooked carrots, comparing different varieties of the vegetable, and how their properties change with heat.

They found that cooking a carrot kills its cells so they can't hold water and this increases the concentration of falcarinol. But heat also softens the walls of the cells so sugar, vitamin C and other compounds such as falcarinol leach out more readily.

Cutting the carrot into pieces before boiling increases the surface area which allows more of the nutrients to leach out of the cell walls into the boiling water.The scientists also asked 100 people to wear a blindfold and compare the taste of carrots that had been cut before cooking and carrots that had been cut after cooking. More than 80 per cent said the carrots that were cut after cooking tasted better.Brandt said:We all want to try to improve our health and diet by getting the right nutrients and eating our five-a-day.

"All you need is a bigger saucepan," she added. However, while the taste trial may have shown an overwhelming vote in favour of cutting after boiling, some experts are not convinced that whether you cut them before or after cooking has any effect on the anti-cancer properties of carrots.Dr Kat Arney, of the charity Cancer Research UK told BBC News that it was eating a healthy balanced diet "rich in a range of fruit and vegetables" that mattered most in reducing cancer risk, and not any one food in particular.

Sources: Newcastle University, BBC News.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today Not to be reproduced without permission of Medical News Today

Gene that stops or suppress cancer plays a role in cancer stem cells

A gene well known to stop or suppress cancer plays a role in cancer stem cells, according to a new study from the University of Michigan Comprehensive Cancer Center. The researchers found that several pathways linked to the gene, called PTEN, also affected the growth of breast cancer stem cells.

Further, by using a drug that interferes with that pathway, the researchers produced an up to 90 percent decrease in the number of cancer stem cells within a tumor.

The study appears in the June issue of PLoS Biology, a journal from the Public Library of Science.

PTEN is the most frequently inactivated tumor suppressor gene in several cancers, including breast cancer, where it is inactivated in about 40 percent of patients. PTEN is linked to poor outcomes and is associated with aggressive cancers resistant to chemotherapy and current targeted therapies.

The U-M researchers deleted PTEN in tumors grown in cell cultures and in mice, and found an increase in the number of stem cells. They also looked at pathways associated with PTEN and reported that a pathway called PI3-K/Akt regulated the cancer stem cell population by activating another stem cell pathway, Wnt, which is also implicated in multiple cancer types.

"Although there has been considerable progress in identifying cancer stem cells in a variety of tumor types, the pathways that drive the transformation of these cells are not well understood," says lead study author Hasan Korkaya, D.V.M., Ph.D., research investigator in internal medicine at the U-M Medical School.. Researchers at U-M were the first to identify stem cells in breast cancer. These cells represent fewer than 5 percent of the cells in a tumor but are believed to be responsible for fueling a tumor's growth and spread. Researchers believe that the ultimate cure of cancer will require killing these cancer stem cells.

In the current study, researchers looked at a drug called perifosine, which inhibits the Akt pathway. Tumors in mice were treated with perifosine or docetaxel, a standard chemotherapy drug. The docetaxel alone showed no effect on the number of cancer stem cells in the tumor. But adding perifosine reduced the cancer stem cell population by up to 90 percent.

What's more, the cells treated with perifosine – either with or without docetaxel – were less likely to grow a secondary tumor, compared to the cells treated with just docetaxel.

"This is most exciting since perifosine and other drugs that target this pathway are currently in clinical development. If cancer stem cells do contribute to tumor relapse, then adding drugs that target these cells may help to make our current therapies more effective," says study senior author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center.

Source: http://www.umich.edu/
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