college of pharmacy

Barriers to health care increase disease, death risk for rural elderly

CORVALLIS, Ore. – A new study of adults ages 85 or older has found that rural residents have significantly higher levels of chronic disease, take more medications, and die several years earlier than their urban counterparts.

The findings were just published in The Journal of Rural Health by researchers from Oregon State University and the Oregon Health & Science University.

The research confirms some of the special challenges facing older populations in rural or remote areas, who often have less access to physicians, long distances to travel for care, sometimes a lower socioeconomic and educational level, and other issues. It also reflects health problems that might have been reduced if they were treated earlier or more aggressively, researchers say.

Data from several different study groups found that rural residents measured significantly higher on the Modified Cumulative Illness Rating Scale, with about an 18 percent higher disease burden.

“It’s been known for some time that health care is harder to access in rural areas, and this helps us better understand the extent of the problem,” said Leah Goeres, a postdoctoral scholar who led the research at the Oregon State University/Oregon Health & Science University College of Pharmacy.

“Many physicians do the best they can in rural areas given the challenges they face,” Goeres said. “But there are fewer physicians, fewer specialists, a higher caseload. Doctors have less support staff and patients have less public transportation. A patient sometimes might need to wait months to see a doctor, and have to drive significant distances. Adverse effects can increase from taking multiple medications.

“These are real barriers to choice and access, and they affect the quality of care that’s available.”

Also worth noting, Goeres said, is that especially in very old populations, illness can lead to more illness and quickly spiral out of control. A patient in an urban setting might receive prompt treatment for a mild ulcer, whereas the same person in a rural setting might have to wait while the condition worsens and may even lead to cancer.

“It’s of particular concern that rural older adults start with more disease burden, which significantly increased over the next five years, but the average number of medications they used decreased over the same time period,” said David Lee, an assistant professor in the OSU College of Pharmacy who oversaw the research.

“This may be due to difficulty accessing health care, leading to more disease burden over time, yet less use of medications,” Lee said. “The opposite trends are seen in urban older adults.”

This research was done in Oregon with three cohorts of older adults, one rural and two urban, and 296 people altogether. It was supported by the Oregon Alzheimer’s Disease Tax Checkoff Fund and the National Institutes of Health.

The findings of the new study include:

  • The rural population of Oregon contains a greater proportion of older adults than the urban population.
  • The use of many medications can be especially risky for people in their 80s and 90s, leading to a concern called “polypharmacy” when a person takes five or more medications.
  • Rural participants were found to use an average of 5.5 medications, compared to 3.7 for urban participants.
  • At baseline measurements, valuable medications to aid bone mineralization were often used less in rural populations, but pain-killing opioids were used more often.
  • Medication use for high blood pressure went up significantly over time for rural populations, but not urban ones, in which their use had already been higher.  
  • The rate of disease accumulation was significant in the rural cohort, and negligible in their urban counterparts.
  • The median survival time of the rural cohort was 3.5 years, compared to 7.1 years for the urban older adults.
  • Risk factors of chronic diseases were low education, poor socioeconomic status, a history of chronic disease, being female, and older age. These factors are associated with a typical rural population.
  • Living with someone, and/or having a large social network are protective factors against chronic disease, and may be more common in an urban or suburban population.
  • Both urban and rural residents used a large number of over-the-counter agents, including vitamins, minerals and herbal supplements.

Increased access to health care, health education, increased supervision from clinicians, and better management of both prescription and over-the-counter medications could all be of value in helping rural residents to live longer and healthier livers, the researchers said in their conclusion.

Media Contact: 

David Lee, 503-494-2258

Advent of recreational marijuana raises wealth of questions – and some answers

CORVALLIS, Ore. – The emergence of the legal recreational use of marijuana, in Oregon and elsewhere, has raised a wide range of questions about this drug – especially after decades of prolonged debates, some groups calling it harmless and others a “gateway” drug that should still be illegal.

At Oregon State University, pharmacological experts are helping to answer these questions. They are speaking to many public and professional groups around the state, as well as OSU pharmacy students, and trying to raise the level of medical knowledge about marijuana, based on the best available science.

That’s a challenge in itself, they say, because despite vehement arguments on both sides of these issues over many years, comparatively little valid scientific research has been done on marijuana. Some key questions remain unanswered, even though there’s evidence the drug has been used by humans for more than 4,000 years, and its use in the U.S. is now expanding significantly as legal restrictions weaken.

That being said, there’s a lot that is known.

First and foremost, today’s commercially available marijuana is not the same product that some may remember from the 1960s or 70s. It is far more potent.

“Marijuana today has a much higher content of THC, its psychoactive component, than it did in the past,” said Jane Ishmael, an associate professor of pharmacology in the OSU College of Pharmacy and a member of the Oregon Public Health Division’s Retail Marijuana Scientific Advisory Committee. Ishmael is an expert on drug action who teaches pharmacy students about drugs of abuse, ranging from alcohol to nicotine or even some over-the-counter and prescription products.

“The average THC content in marijuana decades ago used to be about 4 percent, but with years of improved cultivation techniques and plant improvements it’s now around 17 percent,” she said. “It’s even higher in some specific strains, meaning that today’s marijuana products can be at least four times stronger. For any older people who are considering use of marijuana again now that’s it’s legal, that’s something they should be aware of.”

An important research finding that’s more recent, Ishmael said, is how this age-old drug actually works.

Studies reported in the 1990s showed that the human body contains many receptor targets for THC and also produces “endocannabinoids.” Normally, the endocannabinoid system plays a role in regulation of appetite, pain control, pleasure and other sensations.

It was discovered that chemicals in marijuana, such as THC, bind to cannabinoid receptors in the brain and modulate the release of other neurotransmitters. These actions explain many of the biological impacts of marijuana for sensations of pleasure, its medicinal potential, and other aspects of neurobiology.

“One thing that people must understand is that marijuana is a recreational drug,” Ishmael said. “We’ve now chosen to make it legal, but like other drugs such as alcohol, that’s not synonymous with saying it’s completely safe and harmless. If people choose to use it, they should understand how it works, what it does, and when or with whom it should not be used.”

Among key points to consider, the experts said:

  • Marijuana use is inappropriate for women who are, or may become pregnant or are nursing. THC can pass directly to the baby during pregnancy and breastfeeding, and may affect the baby. There is no known safe amount of marijuana use during pregnancy.
  • For similar reasons, the laws restricting retail marijuana use to those over 21 years of age are important.
  • Marijuana, as many users will attest, causes feelings of relaxation, pleasure, or a stimulated appetite.
  • Marijuana can cause immediate difficulties in thinking and concentrating, dry mouth, blurred vision, increased heart rate and blood pressure, and feelings of anxiety or panic.  
  • Marijuana can impair coordination, slow reaction times, change perceptions of time, danger, and lowers the perception of risk. These issues, along with changes in the ability to think and concentrate, are the clear reasons why it should never be used when driving, riding a bike or operating dangerous equipment.
  • For similar reasons, a person should not ride in a vehicle, or let others ride, if it’s known the driver is under the influence of marijuana. 
  • The effects of marijuana, and the time it takes to clear the body, vary with the individual and mode of use. It has an effect much more quickly if inhaled or vaporized, and most impacts usually wear off after three to four hours when used this way.
  • If marijuana is eaten, as it is sometimes combined with foods to produce what are known as edibles, the effects will typically take longer to start and can last longer, up to 10 hours after eating.
  • Any use of marijuana in a food or candy is a common-sense parental concern in a household where children may be present. Marijuana can make children sick and should always be kept out of sight and reach of children.
  • Although THC is not believed to be a carcinogen, marijuana smoke contains the same cancer-causing chemicals as tobacco smoke, yet the health risks from second-hand exposure to marijuana smoke have been much less studied. Heavy smokers of marijuana can experience chronic bronchitis, including a chronic cough, sputum production and wheezing.
  • Considerable caution should be taken when marijuana is used in conjunction with other prescription medications that act on the central nervous system, such as drugs that have a sedative effect, or with medicines that are prescribed to treat mental illness.
  • Even though the psychoactive effects of marijuana may wear off in a few hours, metabolites from its use can still be detected in the blood or urine for up to three weeks – an issue as it relates to employers that forbid its use, or the complex legal issues of driving under the influence of marijuana.

Some reliable information is now emerging about the medicinal use of marijuana to improve symptoms in a variety of chronic conditions, the researchers said.

There is evidence that marijuana can aid with some types of pain control, such as painful muscle spasms associated with multiple sclerosis and neuropathic pain. It can also help relieve nausea and vomiting associated with chemotherapy, although other drugs are now available with similar effectiveness for that purpose. And it has been shown to improve quality of life in patients struggling with loss of appetite and maintaining body weight, including AIDS patients.

“Frankly, there’s still a lot we don’t know,” Ishmael said. “Marijuana contains more than 400 chemicals and we’ve focused most research just on one of them. Hopefully some future research will help better inform us about the complete range of effects, whether positive or negative.”

Roberto Linares, a senior instructor in the OSU College of Pharmacy who is also on the Oregon Board of Pharmacy, said that the legalization of marijuana will pose many challenges for medical experts in the near future.

“Pharmacies have not yet shown interest in distributing it, in part because that could conflict with the federal laws that apply to their operation,” Linares said. “But people will be coming to their doctors, to their pharmacists and other health professionals, with a lot of reasonable questions if they choose to use legalized marijuana. That’s one reason we’re trying to put out as much valid information as we can.”

Another issue almost completely unexplored, the researchers said, is the interaction of marijuana with many other legal medications. Entire books and computer programs exist with most drugs to help pharmacists analyze precisely how they might interact with another drug. With marijuana, that’s mostly a blank page.

“One other thought that people should consider is that everyone is an individual,” Ishmael said. “People’s reactions to drugs vary widely, it’s not easily predictable. With some, the effects of marijuana use will be much more intense than with others. That should be kept in mind by anyone who is considering its use.”

Media Contact: 

Jane Ishmael, 541-737-5783

Single-agent phototherapy system offers significant new tool to fight cancer

ORLANDO, Fla. - Researchers at Oregon State University today announced an important advance in the field of cancer imaging and phototherapy, using a single-agent system that may ultimately change the efficacy of cancer surgery and treatment around the world.

The newest approach developed at OSU uses a single chemical compound, silicon naphthalocyanine, which has both diagnostic and therapeutic value. It makes cancer cells glow when exposed to near-infrared light, so a surgeon can identify the cancer and more effectively remove it. At the same time, this compound creates heat and reactive oxygen species within any remaining cancer cells, killing them.

In tests completed with laboratory animals, tumors were completely eradicated without side effects, and did not return.

The findings were presented today at the annual meeting of the American Association of Pharmaceutical Scientists in Orlando, Florida, and were also recently published in Chemistry of Materials, a publication of the American Chemical Society.

When perfected, researchers believe that the evolving field of phototherapy may become a new and promising addition to the three primary ways that most cancer is treated today: surgery, radiation and/or chemotherapy.

Phototherapy has the potential to make some of those approaches more effective than they already are. Since this is a different form of therapy, however, it may have special value with cancers that have formed resistance to chemotherapeutic drugs, or present other problems that can’t be managed with existing therapies.

"We've now developed an improved formulation that’s biodegradable, simple, robust and reproducible," said Olena Taratula, a research assistant professor in the Oregon State University/Oregon Health and Science University College of Pharmacy, and lead author on the published study.

"This system that can make cancer cells glow is like giving the surgeon an extra pair of eyes," she said. “And the compound we're working with now is inexpensive and appears effective at killing any cancer cells that remain."

Research so far has studied ovarian cancers in laboratory animals, but the researchers said that conceptually the treatment may also be useful for other solid tumors. There were no apparent side effects on animals tested.

The system that helps deliver the silicon naphthalocyanine to cancer cells is an alternative to a dendrimer-based delivery system reported earlier this year, and uses a copolymer called PEG-PCL as the biodegradable carrier. The carrier causes the silicon naphthalocyanine to accumulate selectively in cancer cells and reach a maximum level in them after about one day, at which point surgery and phototherapy treatment would be done. The compounds are then naturally and completely excreted from the body.

"A single-agent based system is simple and very good at targeting only cancer tumors and should significantly improve outcomes,” said Oleh Taratula, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, who presented this work today at the American Association of Pharmaceutical Scientists. “It’s small, nontoxic and highly efficient."

In continued research with the OSU College of Veterinary Medicine, the treatment will be used on dogs with actual cancerous tumors, before eventually moving on to human clinical trials.

"Our strategy provides cancer imaging with a single-agent theranostic nanoplatform and subsequent phototherapeutic treatment with great potential for clinical translation," the researchers wrote in their conclusion.

Collaborators on the research include Oleh Taratula and Adam Alani, the corresponding authors and assistant professors in the OSU College of Pharmacy; and Shay Bracha, a veterinary oncologist, and Milan Milovancev, a veterinary surgeon from the OSU College of Veterinary Medicine. The work has been supported by the OSU College of Pharmacy, the OSU Venture Development Fund, OSU General Research Fund and the Medical Research Foundation of the Oregon Health and Science University.

Media Contact: 

Oleh Taratula, 503-346-4704

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Phototherapy system
Phototherapy system

Vitamin D, xanthohumol may offer new approach to obesity epidemic

CORVALLIS, Ore. – A growing body of evidence suggests that two natural compounds, vitamin D and xanthohumol, have the ability to address imbalances in gut microbiota that may set the stage for obesity and metabolic syndrome - problems that affect about one out of every three adults in the United States.

To explore and identify the specific mechanisms by which these compounds have beneficial effects, researchers in the Linus Pauling Institute at Oregon State University have received a new five-year, $2.64 million grant from the National Institutes of Health.

The possible payoff of this research, they say, may be an entirely new way to reduce or prevent some of the major diseases that are killing millions of people every year, such as heart disease and type-2 diabetes.

The new approach would attempt, using high dose supplementation, to prevent disease from developing, instead of treating it after the fact.

“The benefits of xanthohumol and vitamin D have been clearly shown in laboratory studies to reduce weight gain and improve gut barrier defenses,” said Adrian Gombart, an associate professor of biochemistry and biophysics in the OSU College of Science, and a principal investigator with the Linus Pauling Institute. “These compounds appear to activate nuclear receptors and pathways that may affect microbe composition, and in the process reduce the damage from metabolic syndrome.”

One study published by OSU researchers two years ago in the Journal of Biological Chemistry found that rats given xanthohumol supplements, which are made from hops, had a 14 percent reduction in weight gain, a 25 percent reduction in plasma fasting glucose, and improved lipid metabolism, compared to a control group of rats that ate the same amount of food. They had a higher rate of fatty acid oxidation and energy metabolism. In simple terms, they burned more fat.

In other studies, higher levels of vitamin D status in humans have been associated with reduced risk of obesity, metabolic syndrome, cancer, infectious diseases, autoimmune diseases, and other health problems.

Other lead investigators on this research include Claudia Maier, an OSU professor of chemistry; Fred Stevens, a professor in the OSU College of Pharmacy and also a principal investigator with the Linus Pauling Institute; and Balz Frei, a distinguished professor of biochemistry and biophysics, and director of the Linus Pauling Institute.

The OSU researchers believe some of the benefits of vitamin D and/or xanthohumol may be a strong increase in the expression of the cathelicidin antimicrobial peptide, or CAMP gene. The hypothesis to be tested in this research, using animal models, is that higher CAMP levels improve gut epithelial barrier function, reduce inflammation, modify gut microbiota and in the process reduce problems with obesity and metabolic syndrome.

“Some of the benefits we’re seeing are fairly clear and dramatic, and we need to better understand the mechanisms that cause them,” Stevens said.

The compounds may also affect liver function, shutting down metabolic pathways that produce fat and glucose, he said.

Vitamin D can be obtained through either the diet or produced by the skin, with adequate exposure to sunshine. Millions of people who live in temperate zones around the world, however, have been found to have inadequate levels of this vitamin, but this can be corrected by taking a supplement.

Xanthohumol, a flavonoid, is also a natural compound and is found in the hops used to make beer. Researchers point out, however, that the levels of xanthohumol being used in this research greatly exceed any amount that could be obtained by drinking beer.

Direct health care costs arising from obesity and related disorders accounts for almost 10 percent of U.S. health care expenditures each year, the researchers said. The health care costs of diabetes alone were estimated in the U.S. at $176 billion in 2012, and it’s one of the leading causes of death in the nation.

Media Contact: 

Adrian Gombart, 541-737-8018

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Xanthohumol in hops

Vitamin D
Vitamin D in milk

System may offer new hope for personalized treatment of eczema

CORVALLIS, Ore. – Pharmaceutical researchers at Oregon State University have developed a new approach to treat eczema and other inflammatory skin disorders that would use individual tests and advanced science to create personalized treatments based on each person’s lipid deficiencies.

A patent has been applied for on this system, which could revolutionize the treatment of eczema if it works as scientists believe it will.

By identifying the specific problems each person has, moisturizers, skin protectants or other products or therapies could be created to address those specific problems.

Aside from powerful steroid treatments that have a wide range of unwanted side effects, the primary existing treatments for eczema are “one size fits all” moisturizing or protective products, with little basis for understanding whether or not that’s what an individual needs. Sometimes such products help, and often they are inadequate.

In 2012 in the United States, about 15 million Americans struggled with eczema, or atopic dermatitis, accounting for about $1 billion in health care costs and 10-20 percent of all visits to a dermatologist.

Eczema and some other skin disorders can be caused by a deficiency in lipids, which are various types of fat in the skin such as ceramides, cholesterol and free fatty acids, according to Arup Indra, an associate professor in the OSU College of Pharmacy and an expert on inflammatory skin disease.

“Lipids in our skin help retain moisture, they act like a blanket that protects against irritation and infection,” Indra said. “You could think of skin cells as the bricks of a wall, but lipids are the mortar that prevent things from getting through the cracks. When they are deficient, problems can develop.”

Part of what makes eczema so difficult to treat, however, is that there are hundreds of lipids, serving various functions as a skin protector, barrier or antimicrobial agent – and every individual has a slightly different lipid composition. Most of the moisturizers now available are just random compositions of lipids that may or may not help address what is missing in a given individual.

The new system created at OSU starts with surprising simplicity. A piece of tape is stuck to the skin and then pulled off, removing with it some skin cells. The painless procedure is totally noninvasive and could be used on anyone from infants to the elderly.

Those skin and lipid samples are then analyzed with sophisticated mass spectrometry in a process created at OSU that literally produces a “lipid fingerprint” – a measurement of that person’s skin and lipid profile. This profile can then be compared against those of healthy individuals, to help identify missing or deficient lipids that may be an underlying cause of the skin disorder.

From that, various products or other therapies can be developed that would help replace or increase the lipids that are deficient in a person. They could be used topically like conventional moisturizers.

OSU’s research, the first of its type, has already shown that the lipid profiles of people with healthy skin often differ markedly from those with eczema or other inflammatory skin disorders. This offers further evidence that altered lipid composition in the skin of eczema patients may be a determinant of disease onset, progression and severity, the researchers said.

“We believe it’s likely that supplementation with the lipids a person specifically needs will help address their skin problems and improve epidermal barrier function, and we plan to test that in continued research,” Indra said.

Findings in this area could also be used in veterinary medicine, the researchers said, since many pets such as cats and dogs also have skin disorders.

Further collaboration and support from private industry is being sought by OSU to help bring these systems more rapidly to availability, through its Office for Commercialization and Corporate Development.

This research has been supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Media Contact: 

Arup Indra, 541-737-5775

Hospice patients, practitioners face quandary about antibiotic use

PORTLAND, Ore. – A survey of hospice programs in Oregon found that only 31 percent had policies for initiating the use of antibiotics, and only 17 percent a policy for when to discontinue them – pointing to a continued uncertainty about the use of such medications in this select group of terminal patients.

The findings, published in the American Journal of Hospice and Palliative Medicine, are among the first to quantify policies for antibiotic use in hospice, where the primary goal is to promote patient comfort and quality of remaining life, but not to prolong it.

A concern highlighted in the research is that antibiotics may have unwanted side effects that can decrease a patient’s comfort, such as nausea, vomiting, diarrhea or yeast infection. It found that such symptoms were observed “sometimes or often” by about half or more of responding hospice programs.

Respondents to the survey did say that they rarely or never use antibiotics to prolong patient’s lives – but 14 percent of programs also reported that this sometimes occurs.

“The lack of specific policies and guidelines about antibiotic use in hospice care reflects the difficulty and uncertainty that still exists in how to manage end-of-life care, even among this group of people who have chosen not to prolong their life,” said Jon Furuno, an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and lead author on the study.

“There may be situations where antibiotic use does improve symptoms and patient comfort,” Furuno said. “On the other hand, antibiotic use is not always benign. They can have adverse events associated with their use, such as gastrointestinal problems. These are difficult decisions in a situation where we’re trying to reduce the number of medications taken at the end of life.”

The development of policies is also complicated by medical uncertainty over exactly how a patient may respond to antibiotic use, Furuno said, and by a paucity of scientific evidence over how well they may work to reduce symptoms in patients who are already terminally ill and often have compromised immune systems.

“The goals of hospice, in general, are fairly well understood by the parties involved, but the application in the field is much more variable,” Furuno said. “There will always be, and should be, flexibility in decisions that vary from patient to patient, and even if we did develop policies they could not be too rigid. But it would help if we could develop some better guidelines to help inform these decisions.”

According to Barbara Hansen, CEO of the Oregon Hospice Association, this study is an important first step toward quantifying the issues related to antibiotic use in hospice patients, and understanding current practices.

“This issue is challenging and problematic, but we all face it, and this research has now laid the groundwork to know what is happening in the field,” Hansen said. “We do need to be more systematic in our approaches, and give hospice practitioners more support in how to talk with patients and their families about antibiotic use.”

A step toward policies, Hansen said, might be guidance about determining whether an infection is actually causing a patient significant discomfort – if not, some may be better left untreated, rather than risk the additional complications that could ensue from treatment. And there may be communication that could be developed earlier to help family members understand the wishes of the patient being care for, she said.

Complicating the problem, the researchers said, is that antibiotic use is so ingrained in contemporary medicine. Previous studies at OSU have shown that 27 percent of hospice patients are still taking antibiotics in the final week of their life. This is a special concern for people who have specifically chosen an end-of-life approach that is focused on protecting the remaining quality of life without aggressively continuing medical treatment.

Hospice is covered by Medicare for people with a life expectancy of less than six months. It often allows people to die in their own homes, helps to reduce medical costs and hospital stays, and its services are now used by more than one third of dying Americans.

Collaborators on this study were from the OSU/OHSU College of Pharmacy and the Oregon Health & Science University. It was supported by the National Institutes of Health.

Media Contact: 

Jon Furuno, 503-418-9361

Advance in photodynamic therapy offers new approach to ovarian cancer

PORTLAND, Ore. – Researchers at Oregon State University have made a significant advance in the use of photodynamic therapy to combat ovarian cancer in laboratory animals, using a combination of techniques that achieved complete cancer cell elimination with no regrowth of tumors.

The findings were just published in the journal Nanomedicine: Nanotechnology, Biology and Medicine, and after further research may offer a novel mechanism to address this aggressive and often fatal cancer that kills 14,000 women in the United States each year.

Ovarian cancer has a high mortality rate because it often has metastasized into the abdominal cavity before it’s discovered. Toxicity and cancer-cell resistance can also compromise the effectiveness of radiation and chemotherapy that’s often used as a follow-up to surgery.

The new approach being developed by researchers from the OSU College of Pharmacy and the University of Nebraska takes existing approaches to photodynamic therapy and makes them significantly more effective by adding compounds that make cancer cells vulnerable to reactive oxygen species, and also reducing the natural defenses of those cells.

“Surgery and chemotherapy are the traditional approaches to ovarian cancer, but it’s very difficult to identify all of the places where a tumor has spread, and in some cases almost impossible to remove all of them,” said Oleh Taratula, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy.

“Photodynamic therapy is a different approach that can be used as an adjunct to surgery right during the operation, and appears to be very safe and nontoxic,” Taratula said. “In the past its effectiveness has been limited, but our new findings may make this technology far more effective than it’s ever been before.”

Using the new approach, a patient is first given a photosensitizing compound called phthalocyanine, which produces reactive oxygen species that can kill cells when they are exposed to near-infrared light. In addition, a gene therapy is administered that lowers the cellular defense against reactive oxygen species.

Both the phthalocyanine and genetic therapy, composed of “small, interfering RNA,” are attached to what researchers call “dendrimer-based nanoplatforms,” a nanotechnology approach developed by OSU researchers. It delivers the compounds selectively into cancer cells, but not healthy cells.

Compared to existing photodynamic therapies, this approach allows the near-infrared light to penetrate much deeper into abdominal tissues, and dramatically increases the effectiveness of the procedure in killing cancer cells.

Using photodynamic therapy alone, some tumors in laboratory animals began to regrow after two weeks. But with the addition of the combinatorial genetic therapy to weaken the cancer cell defenses, there was no evidence of cancer recurrence. During the procedures, mice receiving the gene therapy also continued to grow and gain weight, indicating a lack of side effects.

“Cancer cells are very smart,” Taratula said. “They overexpress certain proteins, including one called DJ1, that help them survive attack by reactive oxygen species that otherwise might kill them. We believe a key to the success of this therapy is that it takes away those defensive mechanisms.”

The overexpression of DJ1, researchers said in their study, is associated with invasion, metastasis, resistance to cancer therapies, and overall cancer cell survival. That excess of DJ1 is silenced by the genetic therapy composed of siRNA.

The findings of this research, Taratula said, could also build upon some other recent advances in photodynamic therapy, in which a different compound called naphthalocyanine could be administered prior to surgery, causing the cancer cells to “glow” and fluoresce when exposed to near-infrared light. This provides a literal road map for surgeons to follow, showing which tissue is cancerous and which is not.

There’s no reason that approach couldn’t be combined with the newest advance, Taratula said, providing multiple mechanisms to improve surgical success and, with minimal side effects, help eradicate any remaining cancer cells that were not completely removed.

“Our study established a prospective therapeutic approach against ovarian cancer,” the researchers wrote in their conclusion. “The tumors exposed to a single dose of a combinatorial therapy were completely eradicated from the mice.”

The studies were supported by the Medical Research Foundation of Oregon and the College of Pharmacy at OSU. Continued research will take place with treatment of malignant tumors on live dogs in the OSU College of Veterinary Medicine, prior to any human clinical tests.

Media Contact: 

Oleh Taratula, 503-346-4704

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Cancer therapy
New cancer therapy

System to boost levels of resveratrol, quercetin could provide new options for cancer therapy

PORTLAND, Ore. – Resveratrol and quercetin, two polyphenols that have been widely studied for their health properties, may soon become the basis of an important new advance in cancer treatment, primarily by improving the efficacy and potential use of an existing chemotherapeutic cancer drug.

Resveratrol, a powerful antioxidant found in red wine and other foods, has already received much attention as a possible explanation for the “French paradox,” a low incidence of cardiovascular disease despite a diet often high in fats.

The new research suggests it may soon have value far beyond that.

In laboratory experiments, researchers at Oregon State University have developed a system to increase the bioavailability of these compounds in the body by using “copolymers” that make them water soluble and allow their injection into the blood stream, creating levels that are far higher than could ever be obtained by diet or oral intake.

The resveratrol and quercetin then appear to reduce the cardiac toxicity of a very widely used cancer drug, Adriamycin. Although highly effective in the treatment of lymphomas, breast, ovarian and other cancers, Adriamycin can only be used for a limited time in humans because of its cardiotoxicity.

The co-administration of these polyphenols might allow much more extensive use of this drug, while at the same time improving its efficacy and demonstrating the polyphenols’ own anti-cancer properties, scientists said.

Findings on this research have been published in the Journal of Controlled Release, by scientists from the College of Pharmacy at Oregon State University and the School of Pharmacy at Pacific University. Both institutions supported the research.

“This has great potential to improve chemotherapeutic cancer treatment,” said Adam Alani, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and lead author on the research.

“The co-administration of high levels of resveratrol and quercetin, in both in vitro and in vivo studies, shows that it significantly reduces the cardiac toxicity of Adriamycin,” Alani said. “And these compounds have a synergistic effect that enhances the efficacy of the cancer drug, by sensitizing the cancer cells to the effects of the drug.”

It’s possible, Alani said, that after further research it could be demonstrated that use of these compounds can completely eliminate the cardiotoxicity of Adriamycin, as they scavenge the toxic free radicals produced by use of this drug. It’s also possible, he said, that administration of these natural polyphenols could have value in cancer therapy by themselves, or in combination with a wider range of other chemotherapeutic drugs.

Resveratrol is a natural compound found in foods such as grapes, red wine, green tea, some fruits, berries and dark chocolate, and has been the subject of dozens of scientific studies for its various health values. Quercetin, also a powerful antioxidant, reaches some of its highest natural levels in capers, some berries, fruits, vegetables and leafy greens.

Although they are still valuable nutrients, these polyphenol compounds when eaten as foods or taken as supplements reach only a tiny fraction of the level that’s possible with direct injection.

And such injection was not possible until the OSU and Pacific University researchers adapted the use of “polymeric micelles” to help make the polyphenols water soluble, so they could be directly inroduced into the body. Such systems have been used before with other compounds, but never these polyphenols.

“There are several advantages with this system,” Alani said. “We can finally reach clinical levels of these polyphenols in the body. We can load both the compounds at one time to help control the cardiotoxicity of the cancer drug, and we can help the polyphenols accumulate in cancer cells where they have their own anti-cancer properties.

“This is like hitting three birds with one stone,” Alani said. “It has great potential.”

Research has already shown that both resveratrol and quercetin appear to be safe at high concentrations in the body, Alani said, although continued research will study that issue, among others. And the fact that such delivery systems, as well as the cancer drugs, are already approved by the FDA should speed the clinical testing and possible medical use of this system, he said.

Media Contact: 

Adam Alani, 503-346-4702

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Cancer therapy
Improved cancer therapy

Pactamycin analogs offer new, gentler approach to cancer treatment


The study this story is based on is available online: http://bit.ly/1PlJvdS


CORVALLIS, Ore. – Researchers at Oregon State University are pursuing a new concept in treatment of epithelial cancer, especially head and neck cancer, by using two promising “analogs” of an old compound that was once studied as a potent anti-tumor agent, but long ago abandoned because it was too toxic.

The analogs are more highly selective than the parent compound, pactamycin, which originally was found to kill all cells, from bacteria to mammals, by inhibiting their protein synthesis.

The pactamycin analogs, which were developed with biosynthetic engineering, also offer a different approach toward cancer therapy – an effort to essentially put cancer cells to sleep, instead of killing them. If successful, this trend may herald a new future in “kinder and gentler” cancer treatments.

Findings on this promising approach to cancer were just published in PLOS One, in work supported by the National Institute of Health and other agencies.

The effects of the pactamycin analogs, called TM-025 and TM-026, were characterized in head and neck cancer cell lines, which cause the eighth most common cancer in the world. But they may have applications to a wider range of cancers, the researchers said, particularly melanoma.

“A traditional view of chemotherapy is that you try to completely kill cancer cells and destroy tumors,” said Arup Indra, an associate professor in the OSU College of Pharmacy and one of the lead authors on the study. “Sometimes this is effective, sometimes not as much. An alternative approach is to cause rapid cell aging and induce premature senescence, which we believe could become a new frontier in cancer drug development.”

A senescent cancer cell, Indra said, doesn’t usually die, but the growth of it and the larger tumor is slowed or stops, and it continues to live in a vegetative state, almost like being asleep. Such an approach can be an alternative way to control cancer without completely killing it, which may help reduce problems with resistance that can quickly develop to chemotherapeutic drugs. And it also avoids some of the most toxic and debilitating side effects of cancer chemotherapies, which are often caused by cell death.

The new findings showed that these analogs of pactamycin largely stopped cancer cell proliferation and growth, causing cells to age and lose their ability to divide and grow. These effects are partly mediated by tumor suppressor p53, which is frequently mutated in human cancers. They do not yet form the basis for a therapy, researchers said, because methods must still be perfected to get them more selectively into the cancer cells.

“With further research we hope to create a nontoxic nanocarrier that could provide targeted delivery of the TM-025 and TM-026 analogs specifically to cancer cells,” said Gitali Indra, an OSU assistant professor and also a lead and corresponding author on the study. “In some cases, such as oral cancer, it may also be possible to use topical treatments. But this approach should have significant promise if we can develop techniques to adequately target the cancer cells.”

The OSU researchers are continuing work to more fully understand the mode of action of these pactamycin analogs. Collaborators on this study include Taifo Mahmud, an OSU professor in the College of Pharmacy, and researchers from the Oregon Health & Science University.


Arup Indra, 541-737-5775

No lotions needed: Many animal species produce their own sunscreen

CORVALLIS, Ore. – Researchers have discovered why many animal species can spend their whole lives outdoors with no apparent concern about high levels of solar exposure: they make their own sunscreen.

The findings, published today in the journal eLife by scientists from Oregon State University, found that many fish, amphibians, reptiles, and birds can naturally produce a compound called gadusol, which among other biologic activities provides protection from the ultraviolet, or sun-burning component of sunlight.

The researchers also believe that this ability may have been obtained through some prehistoric, natural genetic engineering.

The gene that provides the capability to produce gadusol is remarkably similar to one found in algae, which may have transferred it to vertebrate animals – and because it’s so valuable, it’s been retained and passed along for hundreds of millions of years of animal evolution.

“Humans and mammals don’t have the ability to make this compound, but we’ve found that many other animal species do,” said Taifo Mahmud, a professor in the OSU College of Pharmacy, and lead author on the research.

The genetic pathway that allows gadusol production is found in animals ranging from rainbow trout to the American alligator, green sea turtle and a farmyard chicken.

“The ability to make gadusol, which was first discovered in fish eggs, clearly has some evolutionary value to be found in so many species,” Mahmud said. “We know it provides UV-B protection, it makes a pretty good sunscreen. But there may also be roles it plays as an antioxidant, in stress response, embryonic development and other functions.”

In their study, the OSU researchers also found a way to naturally produce gadusol in high volumes using yeast. With continued research, it may be possible to develop gadusol as an ingredient for different types of sunscreen products, cosmetics or pharmaceutical products for humans.

A conceptual possibility, Mahmud said, is that ingestion of gadusol could provide humans a systemic sunscreen, as opposed to a cream or compound that has to be rubbed onto the skin.

The existence of gadusol had been known of in some bacteria, algae and other life forms, but it was believed that vertebrate animals could only obtain it from their diet. The ability to directly synthesize what is essentially a sunscreen may play an important role in animal evolution, and more work is needed to understand the importance of this compound in animal physiology and ecology, the researchers said.

Collaborators on this research were Robert Tanguay and Alan Bakalinsky from the OSU College of Agricultural Sciences and Andrew Karplus from the OSU College of Science. The study was supported by the OSU College of Pharmacy and the National Institutes of Health.

Media Contact: 

Taifo Mahmud, 541-737-9679

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