Breaking News
January 16, 2019 - Questions to ask your doctor about post pregnancy care: MedlinePlus Medical Encyclopedia
January 16, 2019 - Neurons with good housekeeping are protected from Alzheimer’s
January 16, 2019 - Is mindfulness worthy of all the hype?
January 16, 2019 - Physical Activity, Any Type or Amount, Cuts Health Risk from Sitting
January 16, 2019 - New understanding in the evolution of human feet
January 15, 2019 - AHA: New Cholesterol Guidelines Put Ethnicity in the Spotlight
January 15, 2019 - Different brain areas linked to smoking and drinking
January 15, 2019 - Henry Marsh shares insights into neurosurgery and more at Dean’s Lecture Series
January 15, 2019 - Want to Live Longer? For Just 30 Minutes a Day, Do Anything Else But Sit
January 15, 2019 - The Current issue of “The view from here” is concerned with Targets
January 15, 2019 - Plain packaging sparked tobacco price rises, new study finds
January 15, 2019 - Sedentary lifestyles can be unhealthy, physical activity can lower risk
January 15, 2019 - Gut microbiome may help prevent development of cow’s milk allergy
January 15, 2019 - Lesbian, gay and bisexual individuals more likely to suffer severe substance use disorders
January 15, 2019 - New England Journal of Medicine Publishes Positive Results of the Pivotal Trial of Cablivi (caplacizumab) for Rare Blood Clotting Disorder
January 15, 2019 - Levels of inflammatory marker (CRP) linked to housing type and tenure
January 15, 2019 - Three gifts I’m glad I gave myself in 2018
January 15, 2019 - Columbia’s Pediatrics Department Names New Vice Chairs, Expands Leadership
January 15, 2019 - US FDA Accepts Regulatory Submissions for Review of Tafamidis to Treat Transthyretin Amyloid Cardiomyopathy
January 15, 2019 - Staying fit can cut your risk of heart attack by half
January 15, 2019 - Vitamin D supplements are of no gain to those over 70, study shows
January 15, 2019 - Scientists create comprehensive new method to predict breast cancer risk
January 15, 2019 - Research shows connection between social media use and impaired risky decision-making
January 15, 2019 - FDA Approves Expanded Use of Adacel (Tdap) Vaccine for Repeat Vaccination
January 15, 2019 - Treating spinal pain with replacement discs made of ‘engineered living tissue’ moves closer to reality
January 15, 2019 - Providers Walk ‘Fine Line’ Between Informing And Scaring Immigrant Patients
January 15, 2019 - Outcomes Poorer for Medicaid Beneficiaries With STEMI
January 15, 2019 - Decorative Products on Foods Can Be Unsafe
January 15, 2019 - A dream of sustainable surgery in Uganda
January 15, 2019 - Study shows how herpes viruses and tumors have learned to manipulate the same ancient RNA
January 15, 2019 - Common Heart, Diabetes Meds May Help Ease Mental Illness
January 15, 2019 - Stress and trauma in earliest years linked to reduced hippocampal volume in adolescence
January 15, 2019 - Scientists identify endogenous activator of sigma-1 receptors in human cells
January 15, 2019 - MAR treatments unlikely to be cause of premature or low birth weight babies
January 15, 2019 - Parental CPTSD increases transmission of trauma to offspring of Tutsi genocide survivors
January 15, 2019 - High-fat diets shown to increase blood pressure
January 15, 2019 - New institute for food safety to be established in Netherlands
January 15, 2019 - Keele University researchers receive £2.4 million grant to help reduce overprescribing of opioids
January 15, 2019 - Synthetic compound reverses mutant p53 aggregate accumulation, study shows
January 15, 2019 - First elder care robot tested in a WSU smart home apartment
January 15, 2019 - Oxford researchers explore relationship between technology use and adolescent mental health
January 15, 2019 - From microbiome research to healthier and sustainable foods
January 15, 2019 - How coaching moms and dads improves infants’ language skills
January 15, 2019 - Precision health approach tapped to identify causes of poverty
January 14, 2019 - DNA origami can accurately measure how antibodies interact with several antigens
January 14, 2019 - Researchers identify multiple new subtypes of most common childhood cancer
January 14, 2019 - Total Fertility Rates Vary by State
January 14, 2019 - Elevated blood lead level in early childhood associated with increased risk of academic problems in school-aged children
January 14, 2019 - Superior technique identified that can block CRISPR gene editing
January 14, 2019 - Turning breast cancer cells into fat cells prevents the formation of metastases
January 14, 2019 - Review examines what influences HIV-positive patients to stay on antiretroviral drugs in Africa
January 14, 2019 - Identifying genetic factors that lead to squamous cell carcinoma
January 14, 2019 - Virtual video visits can replace office visits without compromising quality of care
January 14, 2019 - Health Highlights: Jan. 10, 2019
January 14, 2019 - Molecular hallmarks of tumor hypoxia across 19 cancer types discovered
January 14, 2019 - Scientists uncover how protein clumps damage cells in Parkinson’s
January 14, 2019 - Physician-scientist’s “indomitable spirit” prevails over personal adversity
January 14, 2019 - King’s researchers receive £1.25 million to investigate fatal eating disorder
January 14, 2019 - UCR researchers uncover how plants sense temperature
January 14, 2019 - Scientists find link between colitis and colon cancer
January 14, 2019 - New skin patch provides long-acting contraceptive protection
January 14, 2019 - Asparagine synthetase deficiency – Genetics Home Reference
January 14, 2019 - Improved stem cell approach could aid fight against Parkinson’s
January 14, 2019 - New class of sleeping pill preserves ability to wake in response to danger signals
January 14, 2019 - Cancer patients are four times more likely to commit suicide
January 14, 2019 - The human brain works in reverse order to retrieve memories
January 14, 2019 - Simple tips can lead to better food choices
January 14, 2019 - Meth’s Resurgence Spotlights Lack Of Meds To Combat The Addiction
January 14, 2019 - TARA Biosystems and Insilico Medicine collaborate to discover novel therapies for cardiac disease
January 14, 2019 - Early life stress in mice affects their offspring behavior
January 14, 2019 - Depression Tied to Worse Asthma Outcomes in Urban Teens
January 14, 2019 - Santa calorie counting
January 14, 2019 - Opiod prescriptions for pet dogs misused by their masters
January 14, 2019 - People with ASD could be better at recognizing regret and relief in others finds study
January 14, 2019 - Conducting ChIP-Seq with Low Cell Numbers
January 14, 2019 - Study explores support and social networks of family carers of people with dementia
January 14, 2019 - At Risk for an Opioid OD? There’s an App for That
January 14, 2019 - Single national electronic health record will help improve care in Canadian hospitals
January 14, 2019 - Study unearths Britain’s first speech therapists
January 14, 2019 - Study reveals nuances of racial inequalities in breast cancer prevention
SLU researcher seeks to find solutions for ‘chemo brain’ symptoms and side effects of opioids

SLU researcher seeks to find solutions for ‘chemo brain’ symptoms and side effects of opioids

image_pdfDownload PDFimage_print

With a pair of RO1 grants from the National Institutes of Health, pain researcher Daniela Salvemini, Ph.D., will embark on two new research projects, studying chemotherapy-induced cognitive impairment, or “chemo brain,” symptoms and unwanted side effects of opioids.

Salvemini, who is professor of pharmacology and physiology at Saint Louis University, has spent her career attempting to understand how pain happens in the body, including chronic pain, cancer pain and chemotherapy-induced pain. She studies pain pathways, the series of interactions between molecular-level components, to understand how pain occurs in order to develop new treatments.

With these awards, Salvemini will expand her work to seek answers to urgent questions surrounding pain and cancer drugs.

Chemotherapy-induced cognitive impairment, or “chemo-brain”

A $2,814,902 grant will allow Salvemini to study a common, debilitating side-effect of chemotherapy called chemotherapy-induced cognitive impairment. She is joined by co-investigators Timothy Doyle, Ph.D., Grant R. Kolar, Ph.D., and Susan Farr, Ph.D. from SLU as well as Jacoba (Cobi) Heijnen, Ph.D., and her team at MD Anderson Cancer Center.

Advances in cancer treatment have led to a sharp increase in the number of cancer survivors, reaching nearly 15 million people in the United States alone. However, in many cases, cancer treatment is associated with severe neurotoxic side effects that not only can disrupt social, educational and occupational functioning, but also decrease survival by interfering with adherence to medication and healthy behavior.

Chemotherapy-induced cognitive impairment (CICI), sometimes called “chemo-brain,” is a major neurotoxic side effect of platinum-based (such as cisplatin) and anthracyclins (such as doxorubicin) chemotherapy drugs that are widely used as part of standard treatment for numerous cancers, including head and neck, testicular, colon, breast, ovarian and non-small cell lung cancers.

CICI is characterized by subtle to moderate cognitive deficits that include decreases in processing speed, memory, executive functioning and attention – side effects which can dramatically impact quality of life for patients, with symptoms persisting well after exposure. With nearly 40 percent of adults projected to be diagnosed with cancer in their lifetime and with CICI rates that are greater 50 percent in cancer patients and survivors, CICI represents a growing public health concern.

Little is known about the mechanisms underlying CICI, and there are no FDA-approved drugs to prevent or cure the condition.

“It is imperative that we understand the underlying causes of this serious adverse drug reaction and identify novel therapeutic approaches with the potential for rapid translation to the clinic,” Salvemini said.

In previous work, Salvemini and her team found that chemotherapy dysregulates endogenous adenosine signaling at one of its receptors, A3AR, leading to neuroinflammatory processes and mitochondrial dysfunction in the central nervous system that contribute to the development and continuation of cognitive impairment.

This grant will explore the use of highly selective A3AR agonists – chemicals that activate the nuclear receptor – as a therapeutic approach to mitigate chemo-brain, providing new molecular insights that will advance our understanding of how chemo-brain occurs.

The researchers also hope their study will show whether CICI can be reversed or turned down once symptoms have appeared by turning on the A3AR receptor. This finding would offer hope that cognitive function could be restored in those cancer survivors who have been already developed CICI.

The team expects that this work will lead to expedited “proof-of-concept” studies, opening the door to a new translational effort in the treatment of chemo-brain to find solutions for this highly unmet medical need.

“We hope that the combination of an A3AR agonist with chemo will prevent dose limiting toxicities, therefore enabling the patient to undergo their full cycle of chemo,” Salvemini said. “More excitingly, we hope that we can reverse the toxicity that has already established thus making a big difference to the quality of life of patients who are cancer free but who are still affected by CICI.

“Imagine patients being able to lead normal lives, putting a shirt or a sock on without feeling pain or the ability to perform a simple daily task because their cognitive impairment is improved or at least not worsened. This is our mission: to make an impact on human suffering. I have dedicated over 25 years to this and I am more motivated than ever.

“I am so grateful to my collaborators and team for their dedication to these efforts.”

Opioids and Pain, Tolerance and Dependence

A $1,722,666 NIH grant will allow Salvemini to study another alarming problem: opioid pain killers that are capable of quelling terrible pain also carry debilitating side effects and significant risk of addiction. She is joined by co-investigators who include Timothy Doyle, Ph.D. and Grant R. Kolar, Ph.D., from SLU as well as Todd Vanderah, Ph.D., and his team at the University of Arizona.

This pain problem sets up a discouraging dilemma for patients and doctors. Opioid pain killers, like hydrocodone and morphine, can ease unbearable pain for those who are suffering. The price, however, can be side effects like nausea, vomiting, drowsiness or sedation, and psychological effects like euphoria, hallucinations or delirium. They also can lead to addiction and cause withdrawal symptoms once halted.

As she searches for new ways to mitigate the side effects of these drugs while preserving their pain killing ability, Salvemini will build on previous work that studied alterations in sphingolipid signaling in the brain.

Salvemini found that these alterations cause the development of several opioid side effects, including pain caused by the chronic use of opioids, called opioid-induced hyperalgesia (OIH), and tolerance, which happens when opioids lose their effects over time, called antinociceptive tolerance, which can lead to increased doses which in turn can contribute to dependence.

Salvemini and her team have identified the molecular cause that drives these unwanted opioid effects. With this grant, they will explore the mechanisms at the cellular and molecular levels that cause OIH, tolerance and dependence.

Salvemini hopes this work will lead to a drug that could be taken together with opioids.

“The idea is to combine a drug that blocks sphingolipid signaling with opioids in order to preserve opioids’ pain-killing properties, but minus their side effects,” Salvemini said.

Source:

https://www.slu.edu/news/2018/october/side-effects-of-cancer-and-pain-medications.php

Tagged with:

About author

Related Articles