Chemotherapy

Dental Researchers Attack Painful Chemo Side Effect

chemo patient

An estimated 400,000 U.S. patients undergoing chemotherapy and radiation therapy each year develop painful mouth sores known as oral mucositis. Researchers across UConn are attacking this common side effect from several angles, with one team working to understand the root causes of the ulcers and another developing a better way to treat them.

Cancer drugs break down the mucous membranes lining the mouth, called oral mucosa, inducing painful lesions that can cause difficulty talking, swallowing, and eating. The pain can become so severe that patients require feeding intravenously or through a stomach tube. Other risks to patients include slower healing, decreased resistance to infection, and general failure to thrive. Secondary infection and potentially life-threatening systemic sepsis have also been reported.

While the pain that oral mucositis causes is certainly of great concern, perhaps the most harmful impact occurs when patients are in such extreme agony that their attending physicians have no choice but to prescribe undesirable dose reductions or treatment breaks in cancer therapy.

One UConn School of Dental Medicine research team published in Springer Nature’s Microbiome the most comprehensive study to date about the patho-physiology of oral mucositis in humans due to the effects of chemotherapy.

The team, led by Dr. Patricia Diaz, associate professor in the Department of Oral Health and Diagnostic Sciences, found that patients who developed the most severe lesions showed suppression of beneficial mouth bacteria and outgrowth of harmful ones.

Further studies are needed to understand which specific microbiome components are detrimental and in what manner they affect the oral mucosa’s ability to withstand a chemotherapy challenge.

Meanwhile, Dr. Rajesh Lalla, professor of dental medicine, is collaborating with UConn Board of Trustees Distinguished Professor of Pharmaceutical Sciences Diane J. Burgess, graduate student Tingting Li, and drug design firm Cellix Bio to develop a new, long-acting topical anesthetic that he hopes will someday replace current methods of treating oral mucositis.

The current first-line therapy at most U.S. hospitals is a mouth rinse containing the local anesthetic lidocaine, providing about 30 minutes of relief. The rinse numbs the entire mouth instead of focusing specifically on the sores, which poses safety concerns since it can inhibit the swallowing reflex. Patients are also often prescribed systemic opioids to treat the pain.

The team has developed an innovative formulation and novel patented compound that allows a long-acting topical anesthetic to be applied directly to sores. The researchers expect the more potent anesthetic should relieve pain for about four hours, eight times as long as the standard mouth rinse.
The compound also exhibits antimicrobial and anti-inflammatory effects naturally delivered by the medium chain fatty acid, which could reduce the severity of lesions from oral mucositis, says Lalla.

Lalla and his collaborators believe they are one to two years away from clinical trials in humans.

Follow-Up – Summer 2018

Research doesn’t stop when we report it. Here are updates on past UConn Health Journal stories:


Glycogen Storage Disease

The world’s first gene therapy clinical trial for Glycogen Storage Disease (GSD) Type Ia is expected to start this year, hosted by the GSD Program at Connecticut Children’s Medical Center and UConn Health, under the direction of Dr. David Weinstein. The FDA–approved trials will be done in conjunction with biopharmaceutical company Ultragenyx.

Spring 2017, “Free to Be Imperfect”


Advancing Surgical Care for Older Adults

UConn John Dempsey Hospital will be one of seven U.S. hospitals to pilot-test newly developed guidelines for improving the quality of surgical care for older adults for the American College of Surgeons’ Coalition for Quality in Geriatric Surgery (CQGS), the American Geriatric Society, and the John A. Hartford Foundation.

Fall 2017, “Pinpointing Risk Factors to Prevent Postoperative Delirium”


Detecting Hearing Loss

Findings presented at the 53rd American Neurotology Society annual spring meeting reveal the first potential biomarker for noise-induced hearing loss. A collaborative study by UConn Health and Sensorion showed changing levels of prestin, an outer hair cell protein, in the blood correlated with the severity of hearing loss.

Fall 2016, “Detecting Hearing Loss, Vertigo Via Blood Tests”


Breast Health

UConn Health assistant professor and breast surgeon Dr. Christina Stevenson has begun providing breast health education in hair salons, funded by the Connecticut Breast Health Initiative. The program aims to reach women in Hartford County who may be at risk for late- stage diagnosis of breast cancer due to health care access barriers.

Fall 2016, “On the Ground for Breast Cancer Awareness”


Skin Cancer Screening

Up to 60 percent of UConn Health patients with a suspicious skin lesion or mole can now avoid invasive biopsies thanks to confocal microscopy technology, according to dermatologist Dr. Jane Grant-Kels. The technology uses a painless laser light to see skin cells on a cellular level and help doctors identify skin cancers, including melanoma.

Summer 2016, “Finding Skin Cancer in a Flash”


Cooling Cap Therapy

Marisa Dolce, a Carole and Ray Neag Comprehensive Cancer Center breast cancer patient, reported keeping 70 percent of her hair as the first UConn Health patient to use optional scalp-cooling technology while undergoing chemotherapy. UConn Health is the only Connecticut institution outside Fairfield County to offer the FDA-approved DigniCap.

Fall 2017, “Cooling Off Chemotherapy’s Side Effects”

Protecting Cancer Patients’ Heart Health

Kim Agnes looks at heart

Dr. Agnes Kim, director of the Cardio-Oncology Program at UConn Health, uses new echocardiography strain imaging to detect signs of potential heart problems in cancer patients, before clinical symptoms are evident.


There are currently more than 15 million cancer survivors in the U.S., and that number is expected to grow to 20 million within 10 years. But as more patients survive cancer, the risk of developing cardiovascular health issues from lifesaving chemotherapy and radiation treatments also is increasing.

In an effort to detect cardiac health risks or conditions early, UConn Health has begun tracking cancer patients with an advanced heart imaging test before, during, and after chemotherapy and radiation therapy.

New echocardiography strain imaging allows cardiologists to hunt for early warning signs of heart muscle function changes or damage within the heart tissue. The in-depth strain analysis is powered by traditional ultrasound technology, which uses high-frequency soundwaves to create a sonogram of the pumping heart.

Dr. Agnes Kim, director of the Cardio-Oncology Program at the Pat and Jim Calhoun Cardiology Center at UConn Health, says it’s very important to monitor cancer patients for any signs of cardiac toxicity.

“Echo strain imaging has been compared to a canary in a coal mine,” she says. “We are so grateful that our cancer patients have access to this latest technology so that we can monitor and intervene early if any warning signs are present.”

Studies have shown that confirming any changes in heart muscle strain can help doctors predict whether a patient is at risk for cardiotoxicity and its side effect of future heart failure. A decline in heart strain of 15 percent or more suggests cardiotoxicity, and doctors may prescribe cardio-protective drugs, such as beta-blockers or ACE inhibitors, or modify the patient’s chemotherapy dosage.

Possible cardiotoxicity side effects from chemotherapy medications include a lowering of overall heart muscle function, which can lead to heart failure, formation of blood clots, or an increase in blood pressure. The side effects of radiation therapy also can lead to damaged heart muscle, heart valves, and arteries, or impact the lining of the heart.

Kim launched the Cardio-Oncology Program in 2014 to ensure UConn Health had an integrated program of oncologists and cardiologists, allowing for coordinated care to address the potential risks to heart health that can arise from cancer treatment.

The program also is studying the presence of serum biomarkers in the blood for predicting whether a cancer patient is at high risk for cardiotoxicity, as well as tracking cancer patients’ long-term heart health to analyze the impact of additional clinical care protections.

Cooling Off Chemotherapy’s Side Effects

UConn Health’s Carole and Ray Neag Comprehensive Cancer Center is the only Connecticut institution outside Fairfield County to offer its breast cancer patients optional scalp-cooling therapy to reduce their chances of hair loss from chemotherapy treatments.

“Chemotherapy-induced temporary hair loss is one of the most common and stressful side effects breast cancer patients experience,” says Dr. Susan Tannenbaum, chief of the Division of Oncology and Hematology at UConn Health. “Anything we can do to limit a woman’s distress while she undergoes breast cancer care is essential for the patient’s overall holistic health.”

Research studies have shown that the FDA-cleared DigniCap, made by Dignitana Inc., is nearly 70 percent effective in reducing hair loss by at least half in breast cancer patients receiving chemotherapy.

While a patient undergoes intravenous chemotherapy treatments, the computerized cooling cap system circulates cooled liquid through a tight-fitting silicone cap. The cooling therapy works to limit chemotherapy’s side effects by constricting the scalp’s blood vessels, which limits the drug’s reach to the hair follicles and also slows the rate of hair cell division.

The technology’s arrival was spearheaded by donations from UConn Health professors Dr. William B. White and Nancy M. Petry, Ph.D., of the Pat & Jim Calhoun Cardiology Center, among others, and grant funding awarded to the UConn Foundation by the CT Breast Health Initiative.

A Path With Less Pain

Genetic Clues Show Which Breast Cancer Patients Are Prone to Post-Treatment Agony

By Kim Krieger

woman chooses between two marked paths


Sickness and pain go together. We think of them as a matched pair, a married couple. Pain signals sickness, sickness causes pain. But this is not always the case. Especially in early stage cancer, often there is no pain — until the patient is treated.

UConn Health researchers have discovered genetic clues that could eventually reveal which people might be vulnerable to post-treatment pain, they reported in the June issue of Biological Research for Nursing.

“We’ll hear women say ‘If I knew the pain would be this bad, I’d have rather died of breast cancer,’” says Erin Young, a UConn Health pain geneticist. Young and her research partners wondered: Can we really call such treatment a “cure”? It would be better if we could know in advance which patients might suffer from which treatments.

Young worked with data collected as part of a broader study involving nurse-scientist and director of UConn’s Center for Advancement in Managing Pain Angela Starkweather, neuroscientist Kyle Baumbauer, and colleagues at the University of Florida and Kyung Hee University in Seoul, South Korea. Young’s analysis found that common variants in two genes contribute to certain symptoms during and after chemotherapy treatment for breast cancer. The results could one day help patients, and their nurses and doctors, make informed treatment decisions and prepare for — or avoid — damage to patients’ quality of life.

The researchers looked at the genetics of 51 women with early-stage breast cancer who had no previous chemotherapy and no history of depression. The women rated their well-being both before and after treatment for cancer, reporting on their pain, anxiety, depression, fatigue, and sleep quality. Young and her colleagues then looked for connections between genes and symptoms.

Can we really call treatment a “cure”? It would be better if we could know in advance with patients might suffer from which treatments.

They looked at three genes in particular: NTRK1, NTRK2, and COMT. These genes are already associated with pain from other research. NTRK1 is connected to rapid-eye-movement sleep (dream sleep), and a specific variant is linked to pain insensitivity. NTRK2 is associated with the nervous system’s role in pain, fatigue, anxiety, and depression. And some common versions of COMT are linked to risks of developing certain painful conditions. The researchers also chose these genes because the variants associated with pain, fatigue, and other symptoms are fairly common, making it possible to get meaningful results from a sample size of just 51 people.

After the analysis, a couple results jumped out at them. Two of the genes, COMT and NTRK2, had significant correlations with pain, anxiety, fatigue, and sleep disturbance. The other gene didn’t.

“I always like having a yes/no answer — if we get some nos, then we know the analysis wasn’t just confirming what we wanted to see,” says Young.

Such a quick look at a small sample of cancer patients can’t give all the answers as to who is going to develop postoperative and post-chemotherapy pain. But what they did find is very suggestive. Some of the gene variants were associated with symptoms before surgery. For example, women with two copies of the A variant of COMT reported more anxiety than other women did. COMT was also linked with pain, both during and after cancer treatment: women with one variant of COMT reported more pain, while women with a different variant reported less.

Fatigue also seems to have a genetic component. Women with one copy of the T variant of NTRK2 reported more posttreatment fatigue than others, and women with two copies reported much more.

Surprisingly, the genes linked to various symptoms worked independently, and didn’t work together to increase overall pain and discomfort. In other words, they weren’t synergistic; they didn’t make each other worse.

The gene variants predicted pain and fatigue above and beyond any differences explained by treatment effects.

The genes’ effects were also independent of the type of treatment the women received; the 51 women followed a number of different types of treatments: different surgeries, different chemotherapies. The gene variants predicted pain and fatigue above and beyond any differences explained by treatment effects. Other experiments by other researchers have shown the COMT variants are connected to the development of skeletal muscle pain.

“So it’s not just our study but the entire literature that suggests COMT could be playing a role in how sensitive you are to many different types of pain,” says Young.

“We are focusing on how we can identify women who are at risk of experiencing persistent pain and fatigue, as these symptoms have the highest impact on reducing quality of life after treatment,” says Starkweather. “It’s a great example of how we can make progress toward the goal of personalized health care. The next piece of the puzzle is to identify the most effective symptom-management interventions based on the patient’s preferences and genetic information.”

Young, Starkweather, and their colleagues say further research, ideally looking at a person’s whole genome, is needed to refine the connections between genetic profiles and the risk of pain. With that knowledge, patients could work together with their care team to develop individualized symptom-management plans. Properly prepared patients would feel more control and less suffering. And perhaps the cure would no longer hurt worse than the disease.

Lab Notes – Summer 2016

Researchers Reveal a Secret of Sepsis

human cell rendering

Severe bacterial infections can push the human body into sepsis, a life-threatening cascade of inflammation and cell death that can be difficult to cure. In the May 19 issue of Cell, immunologist Vijay Rathinam and colleagues at UConn Health proposed an explanation for how bacteria trigger such a dangerous reaction: The human cells aren’t really being invaded. They just think they are, at least when sepsis is caused by gram-negative bacteria. Gram-negative bacteria secrete vesicles of lipopolysaccharides (LPS) that can get inside human cells and set off alarms. When the cell detects the LPS, it thinks a bacterium has slipped past its defenses and self-destructs, spilling inflammatory cytokines that prompt the bacteria to emit more LPS, setting off a vicious cycle.


Nanoparticles: guided missiles for drug delivery

Powerful drugs such as chemotherapy and steroids can be devastatingly effective against their intended targets — but they have a tendency to devastate other, healthy body systems as well. UConn chemist Jessica Rouge is working to make these medications more discriminating in their action by bundling them into guided nanoparticles. Her lab is developing aptamers, molecules that bind to a specific target proteins or cell receptors, that can be attached to the nanoparticles to guide them straight to damaged or diseased cells. This approach could help cancer patients avoid the worst side effects of chemotherapy. It could also be useful for asthmatics who need steroidal anti-inflammatory drugs. With this strategy, the drugs could be sent straight to the lungs, side-stepping side effects completely.


Walnuts May Improve Your Colon Health

a walnut in its shell

Eating walnuts may change gut bacteria in a way that suppresses colon cancer. A team of researchers from UConn Health and The Jackson Laboratory for Genomic Medicine found that mice that ate 7-10.5 percent of their total calories as walnuts (about an ounce per day for humans) developed fewer colon cancers. Walnuts are packed with compounds known to be important nutritionally, but it may be as a whole food that they pack the most significant anti-cancer punch against colon cancer, the third most common cancer in the world. The research, supported in part by the California Walnut Commission and the American Institute for Cancer Research, was published May 23 in the journal Cancer Prevention Research. UConn Health Center for Molecular Medicine cancer researcher Dan Rosenberg and colleagues are now working on a long-term study in humans.


Congestive Heart Failure plus Type 2 Diabetes Worse Than We Knew

Diabetes blood Sugar monitor and test strip

Data from more than 5,300 patients with Type 2 diabetes has shown that these patients face a one-in-four chance of dying within 18 months of being hospitalized for congestive heart failure, according to the global EXAMINE study, led by UConn Health professor of medicine Dr. William B. White. Patients with Type 2 diabetes have two to three times the heart disease risk of the general population. White hopes the results inspire patients and doctors to focus more on preventing cardiovascular disease. The findings were presented June 11 at the American Diabetes Association’s (ADA) annual meeting in New Orleans and published online in the ADA journal Diabetes Care.