Breaking News
February 19, 2019 - Scientists untangle how microbes manufacture key antibiotic compound
February 19, 2019 - Greater primary care physician supply associated with longer life spans
February 19, 2019 - HIV-1 protein suppresses immune response more broadly than thought
February 19, 2019 - For 2020 Dem Hopefuls, ‘Medicare-For-All’ Is A Defining Issue, However They Define It
February 19, 2019 - KU professor discusses promise of brain-computer interface to aid, restore communication
February 19, 2019 - Early marker of cardiac damage triggered by cancer treatment identified
February 19, 2019 - Antidepressant drug could save people from deadly sepsis, research suggests
February 19, 2019 - CRISPR technology creates pluripotent stem cells that are ‘invisible’ to the immune system
February 19, 2019 - Midlife Systemic Inflammation Linked to Later Cognitive Decline
February 19, 2019 - Therapy derived from parasitic worms downregulates proinflammatory pathways
February 19, 2019 - Antimicrobial reusable coffee cups are less likely to become contaminated with bacteria, study shows
February 19, 2019 - Harnessing the evolutionary games played by cancer cells to advance therapies
February 19, 2019 - AHA News: Heart Transplant Survivor Gets Wedding Proposal at Finish Line
February 19, 2019 - HIV hidden in patients’ cells can now be accurately measured
February 19, 2019 - Research finds reasons for sudden cardiac death in patients with stable ischemic disease
February 19, 2019 - New protocol could help physicians to rule out bacterial infections in infants
February 19, 2019 - Women experiencing miscarriage should be offered treatment choices
February 19, 2019 - New protocol can help identify febrile infants at low risk for serious bacterial infections
February 19, 2019 - Innovative way to block HIV runs into a roadblock
February 19, 2019 - Springer Nature with BCRF conduct pilot project to make their research datasets more accessible
February 19, 2019 - Study finds neuromelanin-sensitive MRI as potential biomarker for psychosis
February 19, 2019 - Improvements in cardiovascular care for elderly save billions in health care costs
February 19, 2019 - Chilean food regulations are changing food perceptions and purchasing habits, study suggests
February 19, 2019 - Index endoscopy results are crucial for assessment of Barrett’s patients
February 18, 2019 - Breast cancer screening age should be lowered to 35
February 18, 2019 - Brain synchronization depends on the language of communication
February 18, 2019 - Drug Company Payments Over Time May Influence Rx Practices
February 18, 2019 - Despite socioeconomic gains, black-white ‘health gap’ remains
February 18, 2019 - Researchers report progress in the treatment of aggressive brain tumors
February 18, 2019 - Scientists discover trigger that turns strep infections into devastating disease
February 18, 2019 - Scanning children’s teeth may predict future mental health issues
February 18, 2019 - Health Highlights: Feb. 14, 2019
February 18, 2019 - New knowledge could help predict and prevent depression
February 18, 2019 - More primary care physicians leads to longer life spans | News Center
February 18, 2019 - Study examines link between supply of primary care physicians and life expectancy
February 18, 2019 - New study assesses screen time in young children
February 18, 2019 - Patented IU discovery to treat ARDS has been optioned to Theratome Bio
February 18, 2019 - Software found to be four times better at monitoring ovarian cancer
February 18, 2019 - Male Y chromosomes not ‘genetic wastelands’
February 18, 2019 - Hormone therapy during gender transition may increase risk for cardiovascular events
February 18, 2019 - NICE renews accreditation for Advanced
February 18, 2019 - FDA Grants Orphan Drug Designation to Amplyx Pharmaceuticals for APX001 for Treatment of Cryptococcosis
February 18, 2019 - Molecule effective in killing tuberculosis bacteria
February 18, 2019 - Columbia researchers unravel why some glioblastomas respond to immunotherapy
February 18, 2019 - Men who are able to do ten push-ups are less likely to have a stroke
February 18, 2019 - Blood-brain barrier disruption could lead to age-related cognitive decline
February 18, 2019 - Combination of PARP inhibitor and immunotherapy results in tumor regression in SCLC mouse models
February 18, 2019 - Heavy smoking could lead to vision loss, study finds
February 18, 2019 - New diagnostic test for malaria uses spit, not blood
February 18, 2019 - New therapeutic molecules show promise in reversing memory loss related to depression, aging
February 18, 2019 - Darla Shine joins anti-vaccination campaigners
February 18, 2019 - New study outlines sex-specific issues in ischemic heart disease
February 18, 2019 - Drug combinations could become first-line treatment for metastatic kidney cancer
February 18, 2019 - Lifetime adversity, increased neural processing during trauma combine to intensify core PTSD symptoms
February 18, 2019 - HRQoL Scores Decrease With Treatment Line in Multiple Myeloma
February 18, 2019 - Convincing evidence that type 2 diabetes is a cause of erectile dysfunction
February 18, 2019 - Study offers implications of advanced age in evaluation, management of ischemic heart disease
February 18, 2019 - Children from homes with flame-retardant sofa have high SVOC concentration in their blood
February 18, 2019 - Art Institute of Chicago announces results of research on five terracotta sculptures
February 18, 2019 - New PET/CT tracer shows high detection rate for diagnosis of acute venous thromboembolism
February 18, 2019 - Smoking may blight immune response against melanoma and reduce survival
February 18, 2019 - How Inactivity and Junk Food Can Harm Your Brain
February 18, 2019 - Diabetes tops common conditions for frequent geriatric emergency patients
February 18, 2019 - Longer-lived sperm produces offspring with healthier lifespans
February 18, 2019 - New dental adhesive prevents tooth decay around orthodontic brackets
February 18, 2019 - New eHealth tool shows potential to improve quality of asthma care
February 18, 2019 - New Australian initiative helps emergency clinicians to improve patient care
February 17, 2019 - Apellis Pharmaceuticals’ APL-2 Receives Fast Track Designation from the FDA for the Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria
February 17, 2019 - Researchers identify faulty ‘brake’ that interferes with heart muscle’s ability to contract and relax
February 17, 2019 - Support from trusted adults can reduce risk of dying in suicidal teens, finds study
February 17, 2019 - Heart attack awareness improved since 2008
February 17, 2019 - Exercise gives a better brain boost to older men than women
February 17, 2019 - New research disproves previous assumptions of how looks influence personality
February 17, 2019 - Cannabis use as a teenager linked to depression later in life
February 17, 2019 - Sinks by Toilets in ICU Patient Rooms Harbor Harmful Bacteria
February 17, 2019 - Cancer cells’ plasticity makes them harder to stop
February 17, 2019 - Young cannabis users have increased risk of depression and suicidal behavior
February 17, 2019 - Tasmanian Devils Likely to Survive Cancer Scourge
February 17, 2019 - Neoadjuvant PD-1 blockade seems effective in glioblastoma
February 17, 2019 - Personal, social factors play role in enabling sustainable return to work after ill health
Compound in citrus oil could reduce dry mouth in head, neck cancer patients | News Center

Compound in citrus oil could reduce dry mouth in head, neck cancer patients | News Center

image_pdfDownload PDFimage_print

The key to retaining salivary function is protecting these rare but critical stem and progenitor cells. That’s tricky because, following radiation therapy, toxic, highly reactive compounds called aldehydes are created in the gland, gumming up cellular function.

Le, the Katharine Dexter McCormick and Stanley McCormick Memorial Professor, who specializes in treating head and neck cancer, said she had spent a decade hearing from her patients about their struggles with dry mouth. “I wanted to do something,” she said.      

Her initial strategy was to try to regenerate salivary stem cells and, while working with these cells, her lab found that they contain high levels of an enzyme called aldehyde dehydrogenase 3A1, or ALDH3A1. The enzyme is a member of the large aldehyde dehydrogenase family of enzymes, proteins that initiate or speed up chemical reactions, that can defang troublesome aldehydes. But ALDH3A1 isn’t a match for the radiation-unleashed aldehydes on its own.      

She needed to find something to amp it up.      

Looking to the East      

Le had met with Mochly-Rosen through SPARK, a program founded and co-directed by Mochly-Rosen, that shepherds basic science discoveries into the clinic. Mochly-Rosen, who is the George D. Smith Professor in Translational Medicine, had been working on aldehyde dehydrogenases for more than a decade and had obtained access to a library of 135 traditional Chinese medicine extracts.     

Many of those extracts have been used as treatments for various ailments in humans for hundreds of years, boosting the likelihood they are safe to use, Mochly-Rosen said.      

Her team found that seven of these 135 extracts boosted ALDH3A1 activity. It was up to Saiki to see if she could break apart these complex natural extracts — from plants including tangerine, lotus and an Asian rhizome known as zhi mu in Chinese — to find out what, exactly, was activating the enzyme.    

“She did the unthinkable, a really amazing achievement. She found the single active ingredient that activates the enzyme, ALDH3A1,” Mochly-Rosen said.     

Admittedly, Mochly-Rosen and Saiki said, a bit of luck and a fair amount of trial-and-error were involved. D-limonene stood out from other compounds in the extracts because it is broken down relatively quickly in the body and has been deemed by the Food and Drug Administration as a food flavor “generally recognized as safe” that has been approved for use as a food additive, Saiki said.   

Saiki said she was pleasantly surprised by her finding. “It’s a very common molecule, and sometimes as a scientist you wonder, Why hasn’t anyone seen this before?” she said. 

Next, they had to see if d-limonene would rev up ALDH3A1 in living cells.      

Testing in mice, and humans

A series of experiments with mouse cells that had been exposed to radiation showed that d-limonene reduced aldehyde concentrations in both adult and salivary stem and progenitor cells. Even when the cells were treated weeks after radiation exposure, d-limonene still improved their ability to recover, repair gland structure and produce saliva. Mice that ate d-limonene and were exposed to radiation also produced more saliva than mice that did not receive d-limonene and were exposed to radiation. The researchers also learned that d-limonene wasn’t likely to boost saliva production so high that mice, or humans, would be drooling — the compound didn’t increase saliva production in mice that hadn’t been exposed to radiation. And they confirmed that d-limonene did not affect tumor growth or interfere with the tumor-shrinking effects of the radiation in mice. 

If it works, then this type of drug would be used safely to prevent dry mouth in patients in the long run.

A further set of experiments pulled back the curtain on d-limonene’s work: It was stopping the expression of messages that trigger the salivary stem and progenitor cells to self-destruct.

Buoyed by these positive results, the researchers wanted to know if the compound had any hope of helping patients. To work, it would have to be active inside the salivary glands. To find out, they launched a phase-0 study, an early clinical trial in a small number of patients to see if d-limonene, taken by mouth in a capsule, would be distributed to the salivary gland. Four participants who were having a salivary gland tumor removed took d-limonene for two weeks before the surgery. When the tissue was examined after it was removed, researchers found high levels of d-limonene, showing that it has the potential to be used therapeutically in humans — it reaches the salivary gland tissue.      

The patients did experience one quirky side effect: citrus-infused burps.  

Next, the team plans to start the clinical trial process, which will take several years and require a multi-institutional collaboration, Le said. “If it works, then this type of drug would be used safely to prevent dry mouth in patients in the long run and make it much easier for patients to tolerate the radiation treatment with an improved quality of life after the treatment,” she said.

The work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.

The study’s other Stanford authors are life science research assistant Hongbin Cao; postdoctoral scholars Lauren Van Wassenhove, PhD, Vignesh Viswanathan, PhD, Dhanya Nambiar, PhD, and Matthew Stevens, PhD; life science researcher Joshua Bloomstein; former postdoctoral scholar Dadi Jiang, PhD; senior research scientist Che-Hong Chen, PhD; clinical research coordinator Amanda Simmons; graduate student Hyun Park; biostatistician Rie von Eyben; Eric Kool, PhD, professor of chemistry; and Davud Sirjani, MD, clinical assistant professor of otolaryngology-head and neck surgery.   

Researchers from the University of California-San Francisco also contributed to the study.

The research was funded by grants from the National Institutes of Health (grant R37AA11147, R01DE025227, P01CA067166, U10CA180816, T32GM089626 and T32DK098132).    

Stanford’s departments of Chemical and Systems Biology and of Radiation Oncology also supported the work. 

 

Tagged with:

About author

Related Articles