Rodent of the Week: Drug shows effect on lung cancer tumors

Small-cell lung cancer is a disease sorely in need of better therapies. Now a study in mice has found a promising drug that may enter clinical trials in humans within a year.

One in five people with lung cancer has small-cell lung cancer. The disease has a poor long-term survival rate because the tumors spread quickly. Previous research has shown that these tumor cells grow faster because they are fueled by a growth hormone called FGF-2.

The study, published this week in the journal Cancer Research, examined a drug called PD173074 because it is known to block the receptor that FGF-2 uses to attach to tumor cells. Given to mice with the disease, the drug eliminated tumors in 50% of cases. Another test showed the compound increased the effect of chemotherapy.

"We urgently need to develop new treatments for this disease," the lead author of the study, Dr. Michael Seckl of Imperial College London, said in a news release. Although small-cell lung cancer "responds to chemotherapy initially, the tumors soon become resistant to treatment and sadly nearly all people with the disease do not survive. ... We hope to take this drug, or a similar drug that also stops FGF-2 from working, into clinical trials next year to see if it is a successful treatment for lung cancer in humans."

— Shari Roan

Photo credit: Advanced Cell Technology, Inc.

Fertility procedures do not delay cancer treatment, study finds

Women under 40 who are diagnosed with breast cancer often face the additional burden of losing their fertility due to the cancer treatment. If treatment is likely to cause future infertility, women may wish to undergo a procedure to harvest eggs to preserve future childbearing options.

A study published this week reassures women and their doctors that fertility procedures can be done in an orderly way that should not delay breast cancer treatment. The findings show the key to timely fertility procedures depends on all the parties involved -- the patient, cancer surgeon, medical oncologist and reproductive specialists -- working together and communicating effectively.

"The burden of facing premature menopause adds to the stress experienced by young cancer survivors," the lead author of the study, Dr. Lynn Westphal of Stanford University, said in a news release. "Our study shows that these procedures, when expedited and appropriately timed, do not delay cancer treatment."

The researchers identified 82 women younger than 40 who were diagnosed with breast cancer. Nineteen of the women underwent egg retrieval, while 63 did not. For the women who underwent egg retrieval, an average of 71 days elapsed between initial diagnosis to chemotherapy compared with 67 days in the women who did not have egg retrieval. The time elapsed between surgery and chemotherapy was also similar in the two groups.

The average age of the women who had underwent egg retrieval was 37, and most of them had not previously given birth. The study is published in the November issue of the Journal of the American College of Surgeons.

-- Shari Roan

Photo: Dr. David Diaz, medical director of the West Coast Fertility Centers in Fountain Valley lifts a canister containing frozen human eggs stored in liquid nitrogen. Credit: Mark Boster / Los Angeles Times.

A proposal for improving cord blood transplants

Roughly one in five hematopoietic stem cell transplants performed to treat blood disorders such as leukemia uses cord blood instead of the traditional bone marrow. Cord blood – harvested from umbilical cords shortly after birth – could be used more often if more of it were available. Nearly 14 million people worldwide have volunteered to donate their bone marrow, while the number of cord blood units available for transplant is just over 380,000.

Dutch researchers may have found a partial solution. In an article published in this week's edition of Proceedings of the National Academy of Sciences, they propose that a relatively simple change in the way donors are matched with recipients could expand the number of optimal matches by up to eighteenfold.

When patients need a bone marrow or cord blood transplant, they are matched with donors who share as many human leukocyte antigens (HLAs) as possible. The immune system checks these proteins to tell whether a cell belongs in the body or is foreign, so the closer the match, the greater the chance the transplant will take.

The researchers examined 1,121 patients who received a unit of cord blood from the New York Blood Center National Cord Blood Program. Only 62, or 6%, got blood that was HLA-matched. The remaining 1,059 patients got mismatched blood.

But by coincidence, 79, or 7%, got blood that was matched in another way – according to noninherited maternal antigens, or NIMAs. These are proteins that patients were exposed to from their mothers before they were born. As a result, the researchers speculated that patients with NIMA matches would tolerate their transplants better and have higher survival rates.

They were right.

Three years after their transplants, patients who didn’t have an HLA match but got NIMA-matched cord blood were 40% less likely to have died than patients who didn’t have either kind of match, according to the study. For the sake of comparison, patients who had an HLA match were 60% less likely to have died than patients without either kind of match.

The difference was especially pronounced in patients who were at least 10 years old. Compared with patients with no match, those with an HLA match were 70% less likely to have died and those with a NIMA match were 60% less likely to have passed away, the study found.

NIMA-matched blood had other benefits too. The transplants engrafted faster than in unmatched patients, and the incidence of graft-versus-host disease was lower. The benefits were greatest for patients who were expected to have the worst outcomes, the researchers reported.

The Dutch scientists said they intend to start using NIMA status to matching patients with cord blood and will track the results to see if these trends hold up. They urged others to do so as well.

Allowing patients to substitute one HLA-matched antigen for a NIMA-matched antigen would boost the number of possible matches by a factor of six, and allowing two substitutions would theoretically boost it as much as 18 times. The team calculated that even a sixfold increase in potential matches was the equivalent of increasing the number of cord blood units available for transplant to more than 2 million.

“Although much work lies ahead, our findings justify changing the match algorithm for CB [cord blood] transplants,” they wrote.

-- Karen Kaplan

Photo: A new matching technique could make the most of limited cord blood supplies. Credit: Los Angeles Times

Drugs that stimulate red-blood-cell formation also stimulate blood clots in the leg

Procrit, Epogen and Aranesp, drugs that are used to stimulate red-blood-cell production in cancer patients made anemic by chemotherapy, increase the risk of venou thromboembolism, the production of blood clots in the legs that can move to the lungs and elsewhere to create potentially lethal illnesses. The new data, published today in the Journal of the National Cancer Institute, do not show that the drugs increase the risk of death, but they also do not show that the drugs benefit patients.

The drugs already have been under fire because of a 2006 study showing that aggressive treatment of patients with them led to a higher risk of death and cardiovascular complications. In 2007, the Food and Drug Administration required a strong warning on the label of the drugs, known collectively as erythropoiesis-stimulating agents, or ESAs, and suggested limiting their use to patients with unusually low red blood counts. In 2006, U.S. sales of the drugs totaled $20 billion, and they represented the largest expenditure for drugs by Medicare Part B. In the two years following the 2006 report, however, sales of Aranesp and Procrit fell 23% to 24%.

Dr. Dawn L. Hershman of the Irving Comprehensive Cancer Center at Columbia University Medical Center and her colleagues studied more than 56,210 patients who were at least 65 years old and who were given chemotherapy for colon, non-small cell lung or breast cancer between Jan. 1, 1991, and Dec. 31, 2002. The patients were identified in the government's Surveillance, Epidemiology and End Results-Medicare database that covers about 14% of the population. The cancers chosen, which also included large B-cell lymphoma, were those that were thought to be most likely to require ESAs.

About 27% of the patients, 15,346, received an ESA. The proportion receiving the drugs increased from 4.8% in 1991 to 45.9% in 2002. Blood clots developed in 14.3% of those who received the drugs, compared with 9.8% of those who did not, the team found. Overall survival was similar in both groups. Perhaps most damning: The rate of anemia-related transfusions did not change over the course of the study, despite the greatly increased use of the drugs. It remained constant at 22%.

Dr. J. Leonard Lichtenfeld, deputy chief medical officer of the American Cancer Society, told Healthday News that "this study is one more in a list of several that suggests the value of ESAs was less than originally hoped, and the side effects were greater than previously understood."

-- Thomas H. Maugh II

'In sickness and in health' has different odds for women than for men

Many people have assumed that men are less likely than women to stick by a seriously ill spouse. That assumption might not say much for men. Yet it appears to be true.

In a study of 515 people diagnosed with cancer or multiple sclerosis, researchers at the Fred Hutchinson Cancer Center in Seattle and elsewhere found an overall divorce or separation rate of 11.6%, about what one would expect in the general population. But women were six times more likely than men to face what the researchers called "partner abandonment." 

Among marriages in which women were the diagnosed partner, 20.8% ended in divorce or separation.

Among marriages in which men were the diagnosed partner, 2.9% ended in divorce or separation.

Each marriage, each patient and each spouse is different, so without further data, it's unsafe to make over-generalizations. But as the researchers point out: "Some studies have in fact suggested that men are less able to undertake a caregiving role and assume the burdens of home and family maintenance compared with women. Thus, a woman becomes willing sooner in the marriage to commit to the burdens of having a sick spouse."

Such a commitment matters. The researchers note that cancer patients who stayed married were less likely to use antidepressants and to be hospitalized -- and more likely to participate in clinical trials and to die at home.

In perhaps the most daunting element of their report, they say in their conclusion: "We believe that these findings apply generally to patients with life-altering medical illness."

The report was published in the Nov. 15 issue of the journal Cancer. Here's the abstract. And the news release.

And for a more personal look at the topic, here's a My Turn essay from author Marc Silver (it refers to an earlier study by one of the same researchers): Will a wife's breast cancer lead to husband's infidelity?

And a perhaps much-needed lighter look, also from Silver: Husbands: How to help a wife through cancer treatment

-- Tami Dennis

Photo: Longer marriages are more likely to weather the diagnosis and illness, researchers found. Credit: Los Angeles Times

Embryonic stem cells may restore brains damaged by radiation

Scientists at UC Irvine and UC San Francisco have found a potential new use for human embryonic stem cells – helping cancer patients recover the cognitive function lost when their brains are treated with radiation.

People with tumors in their head or neck often undergo radiation therapy after the cancer is surgically removed. That radiation helps kill off any malignant cells left behind. But it can also debilitate the region of the brain called the hippocampus, which is responsible for learning, memory and processing of spatial information. It is also one of only two areas in the brain known to produce new neurons.

The UC researchers wondered whether embryonic stem cells could pick up the slack. In their pluripotent state, they have the potential to grow into any type of cell in the body. When injected into the hippocampus, would they naturally replace neurons damaged or killed by radiation therapy?

To find out, they radiated the heads of 18 rats. Two days later, six of those rats got two injections of human embryonic stem cells directly into the hippocampus.

After four months, the researchers used a standard test to measure the rats’ cognitive abilities. They placed the animals in an arena with two Lego blocks – borrowed from the son of senior researcher Charles Limoli – and were allowed to explore for as long as they liked.  When they were done, the researchers took the rats out of the arena and moved one of the blocks. Five minutes later, the rats went back in.

All of the animals studied both of the blocks, but the rats that were treated with stem cells spent significantly more time nosing around the one that had been moved. They did so, the researchers say, because they remembered where it used to be and thus were curious about its new position. In fact, they spent almost as much time investigating the block as did a group of control rats that were never subjected to any radiation. But the radiated rats that didn’t get stem cells lost roughly half of their cognitive function, according to the study, published in this week's edition of Proceedings of the National Academy of Sciences.

The scientists tested the rats again 24 hours later and got similar – though less pronounced – results.

When the tests were over, the researchers euthanized the rats and studied their brains. Sure enough, the stem cells had grafted into the hippocampus, where they grew into neurons and another kind of brain cell called astrocytes. In the four months that they were in the rat brains, the stem cells didn’t appear to grow into tumors, though that might have happened if the rats lived longer.

The results suggest that embryonic stem cells could spare cancer patients much of the short-term memory loss that results from cranial radiation and perhaps boost long-term memory as well, the researchers wrote. But several hurdles would have to be cleared before it could be tried in people.

Instead of using embryonic stem cells – which many people object to because they are derived from embryos – patients could be treated with induced pluripotent stem cells. Better known as iPS cells, these reprogrammed cells have been found to behave almost exactly like embryonic stem cells in a variety of laboratory tests. They could be custom-made for cancer patients, reducing the risk that the stem cell transplants would be rejected. But more research is needed to ensure that they would not form new tumors.

“Any treatments showing promise at reversing this are worthy of pursuit,” Limoli, an associate professor of radiation oncology at UCI, said in a statement.

The experiments were funded by the National Institutes of Health and the California Institute for Regenerative Medicine.

-- Karen Kaplan

Photo: These human embryonic stem cells restored cognitive function to rats whose brains were damaged by radiation. Credit: Munjal Acharya / UCI

Breast density can influence cancer recurrence, study finds

It's becoming increasingly clear that women should learn, as part of an overall risk-assessment for breast cancer, whether they have dense breast tissue. Not only is it harder to detect a tumor in dense breast tissue, studies show that the risk of breast cancer is increased up to six times in women with the highest breast density scores compared with women with the lowest breast density scores.

Now a study suggests breast density may play a role in determining the best treatment strategy for women diagnosed with breast cancer. Researchers at the Women's College Research Institute in Toronto evaluated the medical records of 335 women who had undergone a lumpectomy for breast cancer. The researchers assessed the breast density of the women, as seen on their mammograms, and monitored them for a recurrence of cancer.

The study found that patients with the highest breast density had a much higher risk of cancer recurrence than did women with the lowest breast density. After 10 years, the women with the highest breast density had a 21% chance of recurrence compared with 5% among the women with the lowest density. Among women who did not receive radiation therapy after the lumpectomy, those with high-density breast tissue had a 40% chance of recurrence.

It may be important for women who undergo lumpectomy to have additional cancer therapies if they have high-density breast tissue, the authors concluded, even though it's a mystery as to why dense tissue is more problematic.

"The biological basis for the associations between mammographic density, breast cancer risk and breast cancer recurrence are not known," they wrote.

The study is published online in the journal Cancer.

-- Shari Roan

Photo: A breast-cancer awareness ribbon is hoisted at the White House last month. Credit: Shawn Thew /  EPA

Rodent of the Week: New use for an old drug

Research can be serendipitous. Sometimes doctors will stumble on an effective medication or they will find a drug they expected to work on one condition actually helps another.

Such is the case with a gonorrhea medication developed in the 1930s. Preliminary evidence published this week shows that the substance, called acriflavine, may work as a cancer therapy. Researchers from Johns Hopkins University discovered that the drug has the ability to stop the growth of new blood vessels, which may then curb tumor growth. Mice who were engineered to develop cancer showed no tumor growth when they were injected with acriflavine daily. The study showed that acriflavine inhibits the function of a protein called HIF-1, which promotes new blood vessel formation.

"Mechanistically, this is the first drug of its kind," Jun Liu, an author of the paper and a professor of pharmacology and molecular sciences, said in a news release. "It is acting in a way that is never seen for this family of proteins."

Researchers at Johns Hopkins continue to explore new uses for old drugs in the school's expansive drug library.

"The more drugs you have, the more possibilities, the higher the chance you rediscover something that will help," Liu said. "Oftentimes, we are surprised that a drug known to do something else has another hidden property."

The study is published in the Proceedings of the National Academy of Sciences.

-- Shari Roan

Photo credit: Advanced Cell Technology Inc.

Experimental HPV vaccine may treat early-stage vulvar tumors

Gardasil and Cervarix help prevent cancer by blocking infections by the most common forms of the human papilloma virus (HPV), but what if cancerous cells have already begun growing? A new experimental HPV vaccine shows promise of reversing the course of the tumor cells in a small clinical trial reported today in the New England Journal of Medicine.

The vaccine is targeted against a condition called vulvar intraepithelial neoplasia, a precursor of vulvar cancer in which lesions appear on the vulva. About three-quarters of the growths are caused by the strain of virus called HPV-16. Existing treatments include topical chemotherapy, laser removal or surgery, but all are frequently unsuccessful. Such lesions progress to cancer in about 3,200 American women each year, killing about 800.

Dr. Gemma Kenter of Leiden University in the Netherlands and her colleagues have been  studying a vaccine composed of synthetic peptides (amino acid chains or fragments of proteins) encompassing specific sites on HPV-16. The peptides are added to an adjuvant that stimulates a stronger immune response to the peptides when they are injected into the body.

Twenty women were vaccinated three or four times each with the preparation. The lesions disappeared completely in nine of the 20 women, including one patient who had been carrying the lesions for 10 years. They had not returned after two years of monitoring. The growths shrank by at least 50% in six of the women. One woman died of an unrelated heart attack. Two of the other women went on to develop full-fledged cancer, and one who showed significant improvement had a relapse.

The primary side effect was the occurrence of bumps at the injection site. Some of the bumps persisted for as long as two years.

The team now plans to test the vaccine in larger numbers of patients. They are also working to develop vaccines that are more potent and that target other strains of HPV as well.

-- Thomas H. Maugh II

Zombies are evolving; these have an agenda

For creatures on the prowl for brains, a growing number of zombies seem especially thoughtful. Or at least less single-minded than usual.

Last weekend, they turned up in Santa Rosa to tout the need for healthcare reform. Here's the Press Democrat story and the YouTube video.

And this Saturday -- yes, yes, Halloween -- they'll be lurching around Silver Lake Reservoir to raise money for brain cancer research. Proceeds from that event, Zombiethon: A Run for Brains, will benefit City of Hope.

Whether you consider the zombie and brain-cancer connection witty or grotesque (here, we didn't agree), find out more at http://www.silverlakezombiethon.blogspot.com/. (There's a costume contest too.)

The zombies-with-a-cause appear to be a slightly more evolved offshoot of the pop-culture-fad-of-the-moment-zombies.

But presumably even the less health-conscious versions -- if they make a habit of the white-face-and-bloody-mouth look -- would want to know about the potential problems with the trappings of their pastime.

Here's a U.S. News & World Report story on the topic of face paint. One day of use is unlikely to do harm, says one expert quoted. But those who make themselves up routinely may have makeup side effects, amid other problems.

-- Tami Dennis