In a study that could help explain the connections between depression and cancer, researchers at the University of Chicago have used an animal model to find, for the first time, a biological link between tumors and negative mood changes.

The team determined that substances associated with depression are produced in increased quantities by tumors and are transmitted to the brain.

Additionally, pathways that normally moderate the impact of depression-causing substances are disrupted when a tumor develops.

The research further showed that tumors induce changes in gene expression in the hippocampus, the portion of the brain that regulates emotion. Although researchers have long known that depression is a common outcome for people diagnosed with cancer, they had not known if it was brought on by a patient learning of the diagnosis or the result of treatments such as chemotherapy. Now a third source may have been identified.

“Our research shows that two types of tumor-induced molecules, one secreted by the immune system and another by the stress axis, may be responsible,” said Leah Pyter, a postdoctoral fellow and lead author of a paper, “Peripheral Tumors Induce Depressive-like Behaviors and Cytokine Production and Alter Hypothalamic-Pituitary-Andrenal Axis Regulation,” which is published in the current issue of the Proceedings of the National Academy of Sciences.

“Both of these substances have been implicated in depression, but neither has been examined over time frames and magnitudes that are characteristic of chronic diseases such as cancer,” she said.

For their research, the team conducted a series of tests on about 100 rats, some of whom had cancer to determine their behavioral responses in tests of emotional state.

“Rats are commonly used to test drugs that are being studied for potential human benefits, such as treating depression,” said Brian Prendergast, Associate Professor of Psychology at the University of Chicago, and the senior author on the study. “In this case, examining behavioral responses to tumors in non-human animals is particularly useful because the rats have no awareness of the disease, and thus their behavioral changes were likely the result of purely biological factors.”

The team used tests commonly used in testing anti-depressants on rats and found that the rats with tumors became less motivated to escape when submitted to a swimming test, a condition that is similar to depression in humans. The rats with tumors also were less eager to drink sugar water, a substance that usually attracts the appetites of healthy rats.

Further tests revealed that the rats with tumors had increased levels of cytokines in their blood and in the hippocampus when compared with healthy rats. Cytokines are produced by the immune system, and an increase in cytokines has been linked to depression.

The team also found that stress hormone production also was altered in rats with tumors. The rats with tumors also had dampened production of the stress hormone corticosterone. The hormone helps regulate the impact of cytokines and reducing its production therefore increases the impact of cytokines.

The project was supported by an American Cancer Society fellowship, an NIH grant and a grant from the Brian Research Foundation.

Source:
William Harms

University of Chicago

A year-long celebration marking the 25th season for the world’s largest grassroots fundraising activity, the American Cancer Society Relay For Life, is underway. The month of May marks the beginning of the 25th “birthday” year of Relay, the Society’s signature fundraising initiative, and 5,000 communities in the United States and 20 other countries will be celebrating and participating in Relay For Life events through the end of August.

Relay For Life started in 1985, when Dr. Gordy Klatt, a colorectal surgeon in Tacoma, Wash., circled a track for 24-hours to raise money for the American Cancer Society. The program has grown from one man’s passion into the world’s largest non-profit fundraising special event and community movement to end cancer, with one in every 100 Americans participating.

Today, more than 3.5 million people worldwide take part in Relay For Life each year, to celebrate those who have battled cancer, remember loved ones lost, and fight back against the disease. Because of those millions of dedicated Relayers, the American Cancer Society is saving lives and helping people celebrate more birthdays.

The funds raised by Relay For Life have played a role in nearly every major cancer research breakthrough in the last 25 years, leading to groundbreaking discoveries into cancer’s causes and cures. As well, Relay has contributed substantially to the American Cancer Society’s funding of crucial prevention and early detection services; numerous, life-enhancing patient support programs; and advocacy initiatives that encourage lawmakers to do their part to defeat cancer, while rallying communities to join the fight.

To participate in Relay’s 25th birthday year celebration and join the movement, consumers can visit http://www.RelayForLife.org, where they will find more information on:

- Joining or starting a team to raise money,
- Volunteering at an event in their community, and/or
- Making a donation to Relayers they know.

The American Cancer Society saves lives by helping people stay well, helping people get well, by finding cures and by fighting back. Relay For Life rallies communities and helps the American Cancer Society work toward its goal of a world with less cancer and more birthdays.

Source
American Cancer Society

SAN DIEGO, May 19 — Early-phase treatment modalities — ranging from a stem cell attack on metastatic cancer to what may be a true silver bullet against pulmonary infection — were highlighted at the annual meeting of the American Thoracic Society.

The studies are all in the pre-clinical stages but could represent “exciting” new approaches to a range of illnesses, according to Beth Laube, Ph.D., of Johns Hopkins University School of Medicine, who moderated a press conference at which the studies were discussed.

The stem cell study combines two separate areas of research, according to Michael Loebinger, M.D., of University College London.

• Explain to interested patients that new ways of delivering drugs may have important clinical applications, but note that this research is in its early stages.
• Note that this research was published in abstract form and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

On one hand, he said, it has been known for some time that mesenchymal stem cells in bone marrow have the ability to home in on and bind to tumor cells.

On the other, he said, researchers have known that the molecule dubbed TNF-related apoptosis-inducing ligand — or TRAIL — kills cancer cells but not normal cells.

Combining the two using genetic engineering, Dr. Loebinger told reporters, the new cells induced programmed cell death in vitro in a variety of cancer cells, including lung, squamous cell, breast, and cervical cancer cells, while leaving normal cells intact.

In mice, Dr, Loebinger said, injections of the cells reduced tumor growth significantly (at P<0.001 compared with sham injections) when the researchers grafted tumor cells into the animals.

And in animals prone to develop lung tumors (similar to human lung metastases), intravenous injections of the engineered cells meant that 38% of the animals did not develop tumors at all, and the rest had significantly reduced (at P=0.03) growth and number of tumors.

“The two different aspects of this therapy have been used in humans,” he said, but not together. TRAIL, for instance, has been used in phase I and II trials and appears to be safe.

The combination,” he said, “is quite promising” and would be applicable to a wide range of cancers.

Dr. Laube said the experiments are “very, very exciting,” not least because of the ability of the cells to seek out and destroy tumor cells wherever they are in the body.

“That’s got to be helpful to patients,” she said.

Another new treatment modality targeted cystic fibrosis. In CF, the ion channel defects reduce airway surface liquid, which results in reduced mucociliary clearance and recurrent infections, said Andrew Hirsh, Ph.D., of Parion Sciences in Durham, N.C.

One treatment that is sometimes used is the sodium channel blocker amiloride (Midamor), but it has several disadvantages, Dr. Hirsh said, including a relatively short effective span that requires frequent use.

Dr. Hirsh was reporting pre-clinical data on a new sodium channel blocker, dubbed GS-9411, that he said was 100 times more potent than amiloride (in terms of the 50% inhibition concentration).

The drug also was able to maintain 85% of sodium channel blockage after multiple washes, compared with less than 10% for amiloride, which should translate to longer effective time in the body, he said.

The drug, delivered as an aerosol, is now in phase I clinical trials with healthy volunteers, Dr. Hirsh said.

Meanwhile, researchers led by Carolyn Cannon, M.D., Ph.D., of Washington University School of Medicine in St. Louis, are studying how to deliver tiny nanoparticles containing silver compounds to lung infections.

So-called silver carbene complexes have been shown to have antibiotic activity and one developed by Dr. Cannon and colleagues — SCC1 — is now the subject of an investigational new drug application, she said.

For technical reasons, that compound can’t be put in nanoparticles, which she and colleagues thought would allow them to reduce the dose and number of doses needed to achieve a clinical effect.

So they synthesized another molecule — dubbed SCC22 — which could be loaded into nanoparticles of L-tyrosine polyphosphate and delivered using a nebulizer.

In mice infected with Pseudomonas aeruginosa, Dr. Cannon said, 100% survived if they were treated intra-nasally with the SCC-loaded particles, while all of the untreated mice died.

The survival advantage left the researchers “surprised and thrilled,” Dr. Cannon said.

With the nano approach, she said, the mice could be given a smaller dose of the compound and be treated only once a day, compared with twice a day for the drug alone.

Although the drug was tested in vivo against P. aeruginosa, Dr. Cannon said, it has been shown in vitro to be “effective against every bacterial species tested to date.”

It has not escaped her notice, she said, that — if the animal studies are replicated in humans — the compounds will be a true silver bullet against bacteria.

The stem cell study was supported by the Medical Research Council of the United Kingdom. Dr. Loebinger said he had no conflicts. The sodium channel blocker study was supported by Parion Sciences. Dr. Hirsh is an employee of the company and holds stock options. The silver study was supported by the NIH and an internal grant from Washington University. Dr. Cannon said she had no conflicts.

Primary source: American Thoracic Society

Source reference:
Hirsh AJ et al. “GS-9411: A Potential Aerosol Pharmacotherapy for CF” Am J Respir Crit Care Med 2009; 179: Abstract 1195.

Additional source: American Thoracic Society

Source reference:
Cannon CL et al. “Nebulized Nanoparticles Loaded with Broad-Spectrum Silver-Based Antimicrobials for Depot Treatment of Pulmonary Infections” Am J Respir Crit Care Med 2009; 179: Abstract 5035.

Additional source: American Thoracic Society

Source reference:
Loebinger MR et al. “On the TRAIL of a Killer: TRAIL-Expressing Mesenchymal Stem Cells Are Able To Target and Eliminate Lung Metastases” Am J Respir Crit Care Med 2009; 179: Abstract 5132.