UC San Diego Health Sciences News

Protein being studied to fight cancer; may cause toxicity in cardiac cells

A study by researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences and the Department of Pharmacology at the University of California, San Diego, shows that a protein called MCL-1, which promotes cell survival, is essential for normal heart function.

Their study, published in the June 15 online issue of the journal Genes & Development, found that deletion of the gene encoding MCL-1 in adult mouse hearts led to rapid heart failure within two weeks, and death within a month.

MCL-1 (myeloid cell leukemia-1) is an anti-apoptotic protein, meaning that it prevents or delays the death of a cell. It is also a member of the BCL-2 family of proteins that regulate mitochondria – the cell’s power producers – and cell death.  Aberrant expression of anti-apoptotic BCL-2 family members is one of the defining features of cancer cells, and is strongly associated with resistance to current therapies.  Thus, these proteins are currently major targets in the development of new therapies for patients with cancer.

But, while MCL-1 is up regulated in a number of human cancers, contributing to the overgrowth of cancer cells, it is found at high levels in normal heart tissue.  Additionally, the researchers found that autophagy – a process which deals with mitochondrial maintenance and is normally induced by myocardial stress – was impaired in mice with MCL-1 deficient hearts. 

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Emergency department (ED) overcrowding has been a major issue nationally for 20 years and continues to increase in severity. To address this issue, a pilot study has been launched at UC San Diego Health System’s ED to use telemedicine as a way to help address crowding and decrease patient wait times. The study is the first of its kind in California to use cameras to bring on-call doctors who are outside of the hospital to the patient in need.

“This telemedicine study will determine if we can decrease wait times while reducing the number of patients who leave the ED without being seen by a physician,” said David Guss, MD, principal investigator and chair of the department of emergency medicine at UC San Diego School of Medicine. “With the ED physicians on site and an added telemedicine physician, patient care may be significantly expedited. If the use of a telemedicine evaluation can be shown to be safe and effective, it may shift how care in the emergency department is delivered.”

The study, called Emergency Department Telemedicine Initiative to Rapidly Accommodate in Times of Emergency (EDTITRATE), brings telemedicine doctors to patients when the ED becomes busy. An offsite doctor is paged who then remotely links to a telemedicine station to see patients. With the aide of an ED nurse, these patients are seen based on arrival time and level of medical need. All patients must sign a consent form to participate in the study. 

Guided by high fidelity sound and video, the telemedicine physician can examine a patient’s eyes, ears, nose, throat and skin, as well as listen to heart and lung sounds through the module. Laboratory and imaging tests can be ordered and results reviewed. Physician ordering and documentation is accomplished through an electronic medical record.  As a final step, the onsite attending physician reassesses the patient to confirm findings and actions, as well as address any unanswered patient questions.  

“Working in an emergency department opened around the clock, you never know who may come through the door, so you are constantly faced with the challenge of matching staffing resources with the demands for care,” said Guss. “Some emergency departments have placed a physician in the triage area to expedite care, however, if there is low demand for service during these times, an underutilized physician creates an unneeded expense.”

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Anorexia nervosa and bulimia nervosa –disorders characterized by extreme eating behavior and distorted body image – are among the deadliest of psychiatric disorders, with few proven effective treatments.

A landmark study, with first author Tyson Oberndorfer, MD, and led by Walter H. Kaye, MD, professor of psychiatry at the University of California, San Diego School of Medicine, suggests that the altered function of neural circuitry contributes to restricted eating in anorexia and overeating in bulimia.  The research, published June 4 in the early on-line edition of the American Journal of Psychiatry, may offer a pathway to new and more effective treatments for these serious eating disorders.

“It has been unknown whether individuals with anorexia or bulimia have a disturbance in the system that regulates appetite in the brain, or whether eating behavior is driven by other phenomena, such as an obsessional preoccupation with body image,” said Kaye, director of the UCSD Eating Disorders Treatment and Research Program.  “However, this study confirms earlier studies by our group and others that establish a clear link between these disorders and neural processes in the insula, an area of the brain where taste is sensed and integrated with reward to help determine whether an individual hungry or full.”

The UC San Diego study used functional MRI to test this neurocircuitry by measuring the brain response to sweet tastes in 28 women who had recovered from either anorexia or bulimia.

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American College of Surgeons’ Commission on Cancer Recognizes Quality Care

UC San Diego Health System is a recipient of the 2012 Outstanding Achievement Award from the American College of Surgeons’ Commission on Cancer. Seventy-nine cancer care programs—three in California—received this national award based on excellence in providing quality care to cancer patients.

“These 79 cancer programs, surveyed in 2012, currently represent the best of the best—so to speak—when it comes to cancer care,” said Daniel P. McKellar, MD, FACS, chair of the Commission on Cancer. “Each of these facilities is not just meeting nationally recognized standards for the delivery of quality cancer care, they are exceeding them.”

Established in 2004, the honor was awarded to only 19 percent of the cancer care programs surveyed in 2012. The award is designed to recognize quality cancer care and to help patients make an informed decision on where to seek superior treatment.

UC San Diego Moores Cancer Center is recognized as an innovative leader in cancer treatment and research. Home to 413 physicians and scientists, it employs a multidisciplinary team approach to patient care that includes surgical oncology, medical oncology, gynecologic oncology, radiation oncology, pathology, diagnostic radiology, interventional radiology, palliative care, integrative medicine, psychology and nutrition.

“This award distinguishes us as part of an elite group of cancer programs in the United States that are being recognized for providing the highest quality cancer care,” said Jason Sicklick, MD, FACS, surgical oncologist and UC San Diego’s cancer liaison physician to the Commission on Cancer. “It highlights our multidisciplinary approach and allows us to share our best practices with other institutions in order to improve patient care not only in San Diego, but nationwide.”

Raul Coimbra, MD, PhD, FACS, is the only trauma surgeon in the western United States recently invited to be part of the Global Alliance for the Care of the Injured (GACI) – a World Health Organization initiative to improve trauma care in low and middle income countries.

“One of the goals of the GACI is to teach standards in trauma care, data collection, injury surveillance and quality improvement,” said Coimbra, chief, Division of Trauma, Surgical Critical Care and Burns at UC San Diego Health System.  “It is crucial that we share our experiences in the United States around the world.  Trauma is a major public health problem, and extending high quality of care to patients worldwide will also improve the way Americans traveling receive health care.” 

As president of the first World Trauma Congress held in Rio de Janeiro last year and president of the World Coalition for Trauma Care (http://www.world-coalition-trauma-care.org/), a collaborative of multiple professional organizations to advance trauma care, education, prevention and systems development, Coimbra is deeply devoted to international outreach.

“Trauma is a disease that exhibits a pattern with causes that can be defined.  It is preventable.  If we treat trauma as a disease, with efforts toward prevention, we’ll save lives and make people and communities safer,” said Coimbra.

Researchers from the University of California, San Diego Department of Pediatrics and Rady Children’s Hospital-San Diego, a research affiliate of UC San Diego School of Medicine, have found a link between multivitamin use and alcohol consumption before pregnancy, uncovering a need for education about the importance of vitamin supplementation, particularly among women who drink alcohol during their childbearing years. The study was published online this month in Alcoholism: Clinical and Experimental Research.

Researchers examined data collected from the Centers For Disease Control and Prevention’s multiple-state Pregnancy Risk Assessment Monitoring System (PRAMS) of more than 100,000 women between 2004 and 2008. The women answered a series of questions about alcohol use before their pregnancies as well as multivitamin supplement use.  The study found women who reported consuming alcohol regularly or binge drinking were significantly less likely to take a multivitamin supplement compared with those who did not report alcohol consumption.

“It’s likely a woman may consume alcohol before she even realizes she’s pregnant, therefore, these findings are significant,” explained Lauren Bartell Weiss, PhD, a postdoctoral research fellow at UC San Diego’s Center for the Promotion of Maternal Health and Infant Development and co-author of the study. “If a woman is drinking alcohol regularly and unintentionally becomes pregnant, not only does her unborn child have a greater risk of being affected by the alcohol, but other studies suggest that alcohol can also alter the metabolism of nutrients and interfere with the nutritional supply to the developing baby.”

Since pregnancy increases the demand for several vitamins and minerals in order to adequately support a developing fetus, Weiss said the alcohol interference with nutritional supply means a woman’s unborn child may also have a greater risk of developing other birth defects, such as neural tube defects, if she hasn’t been taking a multi-vitamin.

“These findings emphasize the need for educating all women of childbearing age, especially those who drink alcohol, about the importance of taking multivitamins regularly whether they’re planning to have children or not,” said Weiss.

As part of a multicenter clinical trial, researchers at University of California, San Diego School of Medicine are evaluating Pexa-Vec (JX-594) to slow the progression of hepatocellular carcinoma (HCC) or liver cancer. Pexa-Vec is a genetically engineered virus that is used in the smallpox vaccine.

“This clinical trial is evaluating a drug already known to be safe as a vaccine. We are applying it as a potential destructive agent for liver cancer,” said Tony Reid, MD, PhD, professor of medicine, UC San Diego School of Medicine and medical oncologist at UC San Diego Moores Cancer Center. “The goal of the trial is to evaluate if Pexa-Vec can extend patients’ survival through its ability to selectively target and kill cancer cells, cut off the tumor’s blood supply, and activate the body’s own immune system to fight the cancer.”

Patients who are eligible for this Phase 2b randomized clinical trial have a diagnosis of HCC and have been found to be unresponsive to sorafenib, the only systemic therapy currently approved by the FDA.

The clinical trial is designed to compare overall survival for patients receiving the drug combined with palliative care (such as hydration, nutrition and pain management) to patients who receive palliation alone with no additional drug treatment.

While Pexa-Vec is derived from vaccinia virus and is similar to smallpox, it doesn’t contain smallpox and cannot cause the disease. The virus was chosen for study because it shows an ability to target cancerous tissues relative to normal tissues.

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